Addressing unmeasured confounding in comparative observational research.

PubMed

Zhang, Xiang; Faries, Douglas E; Li, Hu; Stamey, James D; Imbens, Guido W

2018-04-01

Observational pharmacoepidemiological studies can provide valuable information on the effectiveness or safety of interventions in the real world, but one major challenge is the existence of unmeasured confounder(s). While many analytical methods have been developed for dealing with this challenge, they appear under-utilized, perhaps due to the complexity and varied requirements for implementation. Thus, there is an unmet need to improve understanding the appropriate course of action to address unmeasured confounding under a variety of research scenarios. We implemented a stepwise search strategy to find articles discussing the assessment of unmeasured confounding in electronic literature databases. Identified publications were reviewed and characterized by the applicable research settings and information requirements required for implementing each method. We further used this information to develop a best practice recommendation to help guide the selection of appropriate analytical methods for assessing the potential impact of unmeasured confounding. Over 100 papers were reviewed, and 15 methods were identified. We used a flowchart to illustrate the best practice recommendation which was driven by 2 critical components: (1) availability of information on the unmeasured confounders; and (2) goals of the unmeasured confounding assessment. Key factors for implementation of each method were summarized in a checklist to provide further assistance to researchers for implementing these methods. When assessing comparative effectiveness or safety in observational research, the impact of unmeasured confounding should not be ignored. Instead, we suggest quantitatively evaluating the impact of unmeasured confounding and provided a best practice recommendation for selecting appropriate analytical methods. Copyright © 2018 John Wiley & Sons, Ltd.

The Combined Effects of Measurement Error and Omitting Confounders in the Single-Mediator Model

PubMed Central

Fritz, Matthew S.; Kenny, David A.; MacKinnon, David P.

2016-01-01

Mediation analysis requires a number of strong assumptions be met in order to make valid causal inferences. Failing to account for violations of these assumptions, such as not modeling measurement error or omitting a common cause of the effects in the model, can bias the parameter estimates of the mediated effect. When the independent variable is perfectly reliable, for example when participants are randomly assigned to levels of treatment, measurement error in the mediator tends to underestimate the mediated effect, while the omission of a confounding variable of the mediator to outcome relation tends to overestimate the mediated effect. Violations of these two assumptions often co-occur, however, in which case the mediated effect could be overestimated, underestimated, or even, in very rare circumstances, unbiased. In order to explore the combined effect of measurement error and omitted confounders in the same model, the impact of each violation on the single-mediator model is first examined individually. Then the combined effect of having measurement error and omitted confounders in the same model is discussed. Throughout, an empirical example is provided to illustrate the effect of violating these assumptions on the mediated effect. PMID:27739903

Confounder summary scores when comparing the effects of multiple drug exposures.

PubMed

Cadarette, Suzanne M; Gagne, Joshua J; Solomon, Daniel H; Katz, Jeffrey N; Stürmer, Til

2010-01-01

Little information is available comparing methods to adjust for confounding when considering multiple drug exposures. We compared three analytic strategies to control for confounding based on measured variables: conventional multivariable, exposure propensity score (EPS), and disease risk score (DRS). Each method was applied to a dataset (2000-2006) recently used to examine the comparative effectiveness of four drugs. The relative effectiveness of risedronate, nasal calcitonin, and raloxifene in preventing non-vertebral fracture, were each compared to alendronate. EPSs were derived both by using multinomial logistic regression (single model EPS) and by three separate logistic regression models (separate model EPS). DRSs were derived and event rates compared using Cox proportional hazard models. DRSs derived among the entire cohort (full cohort DRS) was compared to DRSs derived only among the referent alendronate (unexposed cohort DRS). Less than 8% deviation from the base estimate (conventional multivariable) was observed applying single model EPS, separate model EPS or full cohort DRS. Applying the unexposed cohort DRS when background risk for fracture differed between comparison drug exposure cohorts resulted in -7 to + 13% deviation from our base estimate. With sufficient numbers of exposed and outcomes, either conventional multivariable, EPS or full cohort DRS may be used to adjust for confounding to compare the effects of multiple drug exposures. However, our data also suggest that unexposed cohort DRS may be problematic when background risks differ between referent and exposed groups. Further empirical and simulation studies will help to clarify the generalizability of our findings.

The ACCE method: an approach for obtaining quantitative or qualitative estimates of residual confounding that includes unmeasured confounding

PubMed Central

Smith, Eric G.

2015-01-01

Background:  Nonrandomized studies typically cannot account for confounding from unmeasured factors.  Method:  A method is presented that exploits the recently-identified phenomenon of  “confounding amplification” to produce, in principle, a quantitative estimate of total residual confounding resulting from both measured and unmeasured factors.  Two nested propensity score models are constructed that differ only in the deliberate introduction of an additional variable(s) that substantially predicts treatment exposure.  Residual confounding is then estimated by dividing the change in treatment effect estimate between models by the degree of confounding amplification estimated to occur, adjusting for any association between the additional variable(s) and outcome. Results:  Several hypothetical examples are provided to illustrate how the method produces a quantitative estimate of residual confounding if the method’s requirements and assumptions are met.  Previously published data is used to illustrate that, whether or not the method routinely provides precise quantitative estimates of residual confounding, the method appears to produce a valuable qualitative estimate of the likely direction and general size of residual confounding. Limitations:  Uncertainties exist, including identifying the best approaches for: 1) predicting the amount of confounding amplification, 2) minimizing changes between the nested models unrelated to confounding amplification, 3) adjusting for the association of the introduced variable(s) with outcome, and 4) deriving confidence intervals for the method’s estimates (although bootstrapping is one plausible approach). Conclusions:  To this author’s knowledge, it has not been previously suggested that the phenomenon of confounding amplification, if such amplification is as predictable as suggested by a recent simulation, provides a logical basis for estimating total residual confounding. The method's basic approach is

Analyzing partially missing confounder information in comparative effectiveness and safety research of therapeutics.

PubMed

Toh, Sengwee; García Rodríguez, Luis A; Hernán, Miguel A

2012-05-01

Electronic healthcare databases are commonly used in comparative effectiveness and safety research of therapeutics. Many databases now include additional confounder information in a subset of the study population through data linkage or data collection. We described and compared existing methods for analyzing such datasets. Using data from The Health Improvement Network and the relation between non-steroidal anti-inflammatory drugs and upper gastrointestinal bleeding as an example, we employed several methods to handle partially missing confounder information. The crude odds ratio (OR) of upper gastrointestinal bleeding was 1.50 (95% confidence interval: 0.98, 2.28) among selective cyclo-oxygenase-2 inhibitor initiators (n = 43 569) compared with traditional non-steroidal anti-inflammatory drug initiators (n = 411 616). The OR dropped to 0.81 (0.52, 1.27) upon adjustment for confounders recorded for all patients. When further considering three additional variables missing in 22% of the study population (smoking, alcohol consumption, body mass index), the OR was between 0.80 and 0.83 for the missing-category approach, the missing-indicator approach, single imputation by the most common category, multiple imputation by chained equations, and propensity score calibration. The OR was 0.65 (0.39, 1.09) and 0.67 (0.38, 1.16) for the unweighted and the inverse probability weighted complete-case analysis, respectively. Existing methods for handling partially missing confounder data require different assumptions and may produce different results. The unweighted complete-case analysis, the missing-category/indicator approach, and single imputation require often unrealistic assumptions and should be avoided. In this study, differences across methods were not substantial, likely due to relatively low proportion of missingness and weak confounding effect by the three additional variables upon adjustment for other variables. Copyright © 2012 John Wiley & Sons, Ltd.

Disease risk score as a confounder summary method: systematic review and recommendations.

PubMed

Tadrous, Mina; Gagne, Joshua J; Stürmer, Til; Cadarette, Suzanne M

2013-02-01

To systematically examine trends and applications of the disease risk score (DRS) as a confounder summary method. We completed a systematic search of MEDLINE and Web of Science® to identify all English language articles that applied DRS methods. We tabulated the number of publications by year and type (empirical application, methodological contribution, or review paper) and summarized methods used in empirical applications overall and by publication year (<2000, ≥2000). Of 714 unique articles identified, 97 examined DRS methods and 86 were empirical applications. We observed a bimodal distribution in the number of publications over time, with a peak 1979-1980, and resurgence since 2000. The majority of applications with methodological detail derived DRS using logistic regression (47%), used DRS as a categorical variable in regression (93%), and applied DRS in a non-experimental cohort (47%) or case-control (42%) study. Few studies examined effect modification by outcome risk (23%). Use of DRS methods has increased yet remains low. Comparative effectiveness research may benefit from more DRS applications, particularly to examine effect modification by outcome risk. Standardized terminology may facilitate identification, application, and comprehension of DRS methods. More research is needed to support the application of DRS methods, particularly in case-control studies. Copyright © 2012 John Wiley & Sons, Ltd.

Disease Risk Score (DRS) as a Confounder Summary Method: Systematic Review and Recommendations

PubMed Central

Tadrous, Mina; Gagne, Joshua J.; Stürmer, Til; Cadarette, Suzanne M.

2013-01-01

Purpose To systematically examine trends and applications of the disease risk score (DRS) as a confounder summary method. Methods We completed a systematic search of MEDLINE and Web of Science® to identify all English language articles that applied DRS methods. We tabulated the number of publications by year and type (empirical application, methodological contribution, or review paper) and summarized methods used in empirical applications overall and by publication year (<2000, ≥2000). Results Of 714 unique articles identified, 97 examined DRS methods and 86 were empirical applications. We observed a bimodal distribution in the number of publications over time, with a peak 1979-1980, and resurgence since 2000. The majority of applications with methodological detail derived DRS using logistic regression (47%), used DRS as a categorical variable in regression (93%), and applied DRS in a non-experimental cohort (47%) or case-control (42%) study. Few studies examined effect modification by outcome risk (23%). Conclusion Use of DRS methods has increased yet remains low. Comparative effectiveness research may benefit from more DRS applications, particularly to examine effect modification by outcome risk. Standardized terminology may facilitate identification, application, and comprehension of DRS methods. More research is needed to support the application of DRS methods, particularly in case-control studies. PMID:23172692

An overview of confounding. Part 1: the concept and how to address it.

PubMed

Howards, Penelope P

2018-04-01

Confounding is an important source of bias, but it is often misunderstood. We consider how confounding occurs and how to address confounding using examples. Study results are confounded when the effect of the exposure on the outcome, mixes with the effects of other risk and protective factors for the outcome. This problem arises when these factors are present to different degrees among the exposed and unexposed study participants, but not all differences between the groups result in confounding. Thinking about an ideal study where all of the population of interest is exposed in one universe and is unexposed in a parallel universe helps to distinguish confounders from other differences. In an actual study, an observed unexposed population is chosen to stand in for the unobserved parallel universe. Differences between this substitute population and the parallel universe result in confounding. Confounding by identified factors can be addressed analytically and through study design, but only randomization has the potential to address confounding by unmeasured factors. Nevertheless, a given randomized study may still be confounded. Confounded study results can lead to incorrect conclusions about the effect of the exposure of interest on the outcome. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

An overview of confounding. Part 2: how to identify it and special situations.

PubMed

Howards, Penelope P

2018-04-01

Confounding biases study results when the effect of the exposure on the outcome mixes with the effects of other risk and protective factors for the outcome that are present differentially by exposure status. However, not all differences between the exposed and unexposed group cause confounding. Thus, sources of confounding must be identified before they can be addressed. Confounding is absent in an ideal study where all of the population of interest is exposed in one universe and is unexposed in a parallel universe. In an actual study, an observed unexposed population represents the unobserved parallel universe. Thinking about differences between this substitute population and the unexposed parallel universe helps identify sources of confounding. These differences can then be represented in a diagram that shows how risk and protective factors for the outcome are related to the exposure. Sources of confounding identified in the diagram should be addressed analytically and through study design. However, treating all factors that differ by exposure status as confounders without considering the structure of their relation to the exposure can introduce bias. For example, conditions affected by the exposure are not confounders. There are also special types of confounding, such as time-varying confounding and unfixable confounding. It is important to evaluate carefully whether factors of interest contribute to confounding because bias can be introduced both by ignoring potential confounders and by adjusting for factors that are not confounders. The resulting bias can result in misleading conclusions about the effect of the exposure of interest on the outcome. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

Effectiveness and confounding factors of penetrating astigmatic keratotomy in clinical practice

PubMed Central

Yen, Chu-Yu; Tseng, Gow-Lieng

2018-01-01

Abstract Rationale: Penetrating astigmatic keratotomy (penetrating AK) is a well-known method to correct corneal astigmatism but rarely be performed nowadays. This article reevaluated the clinical effectiveness and confounding factors of penetrating AK. Patient concerns: Penetrating AK has been introduced to serve as one alternative operation for astigmatism correction, and is thought to have the potential advantage of being more affordable and easy to perform. The purpose of our study is to evaluate the effectiveness and confounding factors of penetrating AK. Diagnoses: The chart of 95 patients with corneal astigmatism (range: 0.75–3.25 diopters [D]) who received penetrating AK from January 2014 to December 2016 was collected. The corneal astigmatism were measured by an autokeratometer (Topcon KR8100PA topographer-autorefractor), and repeated with manual keratometer in low reproducibility cases. Interventions: All patients received penetrating AK by an experienced ophthalmologist (Dr. Gow-Lieng Tseng, MD, PHD) in the operation room. Among which, 66 patients received penetrating AK with phacoemulsification simultaneously (group A), whereas 29 patients received penetrating AK at least 3 months after phacoemulsification (group B). After excluding the patients combined with other procedures or lost followed up, 79 patients are remaining for analysis. The outcome was evaluated by net correction, the difference between preoperative corneal astigmatism (PCA) and residual corneal astigmatism (RCA). Two sample t tests and Pearson test were used for effectiveness evaluation. For confounding factors, multivariate linear regression was used for statistical analysis. Outcomes: The mean preoperative and postoperative refractive cylinders were 1.97 ± 0.77 and 1.08 ± 0.64 D, respectively, in group A and 2.62 ± 1.05 and 1.51 ± 0.89 D in group B. There were no statistically significant differences in net correction between these two groups (0.9 ± 0.66 vs

Interpretational Confounding or Confounded Interpretations of Causal Indicators?

ERIC Educational Resources Information Center

Bainter, Sierra A.; Bollen, Kenneth A.

2014-01-01

In measurement theory, causal indicators are controversial and little understood. Methodological disagreement concerning causal indicators has centered on the question of whether causal indicators are inherently sensitive to interpretational confounding, which occurs when the empirical meaning of a latent construct departs from the meaning…

Breast milk and cognitive development—the role of confounders: a systematic review

PubMed Central

Walfisch, Asnat; Sermer, Corey; Cressman, Alex; Koren, Gideon

2013-01-01

Objectives The association between breastfeeding and child cognitive development is conflicted by studies reporting positive and null effects. This relationship may be confounded by factors associated with breastfeeding, specifically maternal socioeconomic class and IQ. Design Systematic review of the literature. Setting and participants Any prospective or retrospective study, in any language, evaluating the association between breastfeeding and cognitive development using a validated method in healthy term infants, children or adults, was included. Primary and secondary outcome measures Extracted data included the study design, target population and sample size, breastfeeding exposure, cognitive development assessment tool used and participants’ age, summary of the results prior to, and following, adjustment for confounders, and all confounders adjusted for. Study quality was assessed as well. Results 84 studies met our inclusion criteria (34 rated as high quality, 26 moderate and 24 low quality). Critical assessment of accepted studies revealed the following associations: 21 null, 28 positive, 18 null after adjusting for confounders and 17 positive—diminished after adjusting for confounders. Directionality of effect did not correlate with study quality; however, studies showing a decreased effect after multivariate analysis were of superior quality compared with other study groupings (14/17 high quality, 82%). Further, studies that showed null or diminished effect after multivariate analysis corrected for significantly more confounders (7.7±3.4) as compared with those that found no change following adjustment (5.6±4.5, p=0.04). The majority of included studies were carried out during childhood (75%) and set in high-income countries (85.5%). Conclusions Much of the reported effect of breastfeeding on child neurodevelopment is due to confounding. It is unlikely that additional work will change the current synthesis. Future studies should attempt to rigorously

Mismeasurement and the resonance of strong confounders: uncorrelated errors.

PubMed

Marshall, J R; Hastrup, J L

1996-05-15

Greenland first documented (Am J Epidemiol 1980; 112:564-9) that error in the measurement of a confounder could resonate--that it could bias estimates of other study variables, and that the bias could persist even with statistical adjustment for the confounder as measured. An important question is raised by this finding: can such bias be more than trivial within the bounds of realistic data configurations? The authors examine several situations involving dichotomous and continuous data in which a confounder and a null variable are measured with error, and they assess the extent of resultant bias in estimates of the effect of the null variable. They show that, with continuous variables, measurement error amounting to 40% of observed variance in the confounder could cause the observed impact of the null study variable to appear to alter risk by as much as 30%. Similarly, they show, with dichotomous independent variables, that 15% measurement error in the form of misclassification could lead the null study variable to appear to alter risk by as much as 50%. Such bias would result only from strong confounding. Measurement error would obscure the evidence that strong confounding is a likely problem. These results support the need for every epidemiologic inquiry to include evaluations of measurement error in each variable considered.

Estimating influenza vaccine effectiveness: Evolution of methods to better understand effects of confounding in older adults.

PubMed

McElhaney, Janet E; Andrew, Melissa K; McNeil, Shelly A

2017-11-01

Older adults are at high risk for serious complications of influenza illness and loss of vaccine-mediated protection. It is increasingly recognized that in addition to age, multiple chronic conditions and associated frailty contribute to the decline in vaccine effectiveness in this population. However, observational studies have been fraught with issues of confounding related to the degree of frailty and functional decline, measures of which are not included in standard administrative health care databases that are used to calculate vaccine effectiveness. This issue has led to the identification of confounding by indication or from "healthy vaccinee" bias, which respectively lead to underestimates or overestimates of influenza vaccine effectiveness. In addition, the sensitivity and specificity of the criteria used to define influenza-like illness declines with increasing age due to atypical presentations of illness and the inability to distinguish between influenza and other respiratory viruses. The test-negative case:control design has emerged as a method to estimate influenza vaccine effectiveness by comparing vaccination rates in those with laboratory-confirmed influenza to those with other acute viral respiratory illnesses. This review provides a perspective on how test-negative case:control study designs and new insights into mechanisms of protection have considerably strengthened influenza vaccination policy decisions for older adults that have historically been undermined by the conclusions of observational studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Doubly robust matching estimators for high dimensional confounding adjustment.

PubMed

Antonelli, Joseph; Cefalu, Matthew; Palmer, Nathan; Agniel, Denis

2018-05-11

Valid estimation of treatment effects from observational data requires proper control of confounding. If the number of covariates is large relative to the number of observations, then controlling for all available covariates is infeasible. In cases where a sparsity condition holds, variable selection or penalization can reduce the dimension of the covariate space in a manner that allows for valid estimation of treatment effects. In this article, we propose matching on both the estimated propensity score and the estimated prognostic scores when the number of covariates is large relative to the number of observations. We derive asymptotic results for the matching estimator and show that it is doubly robust in the sense that only one of the two score models need be correct to obtain a consistent estimator. We show via simulation its effectiveness in controlling for confounding and highlight its potential to address nonlinear confounding. Finally, we apply the proposed procedure to analyze the effect of gender on prescription opioid use using insurance claims data. © 2018, The International Biometric Society.

Effect modification of the association between temperature variability and daily cardiovascular mortality by air pollutants in three Chinese cities.

PubMed

Luo, Kai; Li, Runkui; Wang, Zongshuang; Zhang, Ruiming; Xu, Qun

2017-11-01

There is limited evidence showing the mortality effects of temperature variability (TV) on cardiovascular diseases. The joint effects between TV and air pollutants are also less well-established. This study aims to assess the effect modification of TV-cardiovascular mortality by air pollutants in three Chinese cities (Beijing, Nanjing and Chengdu). Data of daily mortality, air pollutants and meteorological factors from 2008 to 2011 was collected from each city. TV was calculated as the standard deviation of daily maximum and minimum temperatures over exposure days. The city-specific effect estimates of TV on cardiovascular mortality were calculated using a quasi-Poisson regression model, adjusting for potential confounders (e.g., seasonality and temperature). An interaction term of TV and a three-level air pollutants stratum indicator was included in the models. Effect modifications by air pollutants were assessed by comparing the estimates of TV's effect between pollutant stratums and calculating the corresponding 95% confidential interval of the differences. Multivariate meta-analysis was conducted to obtain the pooled estimates. The data showed that TV was associated with increased risk of cardiovascular mortality, especially for longer TV exposure days (0-8 days, TV08). This association was still observed after adjusting for air pollutants on current day or the previous two days. Stronger estimates were observed in females, but no significant difference between males and females was detected, indicating the absence of evidence of effect modification by gender. Estimates of TV-cardiovascular mortality varied across two season periods (warm and cool season) and age groups, but the evidence of effect modification by age and seasons was absent. Regarding the effect modification of TV-cardiovascular mortality association by air pollutants, a significant effect modification was identified for PM 10, but not for NO 2 and SO 2 in the whole population for all TV

Evaluation of uncontrolled confounding in studies of environmental exposures and neurobehavioral testing in children.

PubMed

Mink, Pamela J; Goodman, Michael; Barraj, Leila M; Imrey, Harriet; Kelsh, Michael A; Yager, Janice

2004-07-01

Neurobehavioral tests are commonly used in studies of children exposed to low-level environmental concentrations of compounds known to be neurotoxic at higher levels. However, uncontrolled or incomplete control for confounding makes interpretation of results problematic because effects of confounders are often stronger than the effects of primary interest. We examined a priori the potential impact of confounding in a hypothetical study evaluating the association of a potentially neurotoxic environmental exposure with neurobehavioral function in children. We used 2 outcome measures: the Bayley Scales of Infant Development Mental Development Index and the Stanford-Binet Intelligence Scale Composite Score. We selected 3 potential confounders: maternal intelligence, home environment, and socioeconomic status as measured by years of parental education. We conducted 3 sets of analyses measuring the effect of each of the 3 confounding factors alone, 2 confounders acting simultaneously, and all 3 confounders acting simultaneously. Relatively small differences (0.5 standard deviations) in confounding variables between "exposed" and "unexposed" groups, if unmeasured and unaccounted for in the analysis, could produce spurious differences in cognitive test scores. The magnitude of this difference (3-10 points) has been suggested to have a meaningful impact in populations. The method of measuring confounders (eg, maternal intelligence) could also substantially affect the results. It is important to carefully consider the impact of potential confounders during the planning stages of an observational study. Study-to-study differences in neurobehavioral outcomes with similar environmental exposures could be partially explained by differences in the adjustment for confounding variables. Copyright 2004 Lippincott Williams and Wilkins

JIM-13-0560 R1: Propensity scores for confounder adjustment when assessing the effects of medical interventions using non-experimental study designs

PubMed Central

Stürmer, Til; Wyss, Richard; Glynn, Robert J.; Brookhart, M. Alan

2014-01-01

Treatment effects, especially when comparing two or more therapeutic alternatives as in comparative effectiveness research, are likely to be heterogeneous across age, gender, co-morbidities, and co-medications. Propensity scores (PSs), an alternative to multivariable outcome models to control for measured confounding, have specific advantages in the presence of heterogeneous treatment effects. Implementing PSs using matching or weighting allows us to estimate different overall treatment effects in differently defined populations. Heterogeneous treatment effects can also be due to unmeasured confounding concentrated in those treated contrary to prediction. Sensitivity analyses based on PSs can help to assess such unmeasured confounding. PSs should be considered a primary or secondary analytic strategy in non-experimental medical research, including pharmacoepidemiology and non-experimental comparative effectiveness research. PMID:24520806

Structural confounding of area-level deprivation and segreation: an empirical example

EPA Science Inventory

The neighborhood effects literature has grown, but its utility is limited by the lack of attention paid to non-random selection into neighborhoods. Confounding occurs when an exposure and an outcome share an underlying common cause. Confounding resulting from differential allocat...

Understanding Confounding Effects in Linguistic Coordination: An Information-Theoretic Approach

PubMed Central

Gao, Shuyang; Ver Steeg, Greg; Galstyan, Aram

2015-01-01

We suggest an information-theoretic approach for measuring stylistic coordination in dialogues. The proposed measure has a simple predictive interpretation and can account for various confounding factors through proper conditioning. We revisit some of the previous studies that reported strong signatures of stylistic accommodation, and find that a significant part of the observed coordination can be attributed to a simple confounding effect—length coordination. Specifically, longer utterances tend to be followed by longer responses, which gives rise to spurious correlations in the other stylistic features. We propose a test to distinguish correlations in length due to contextual factors (topic of conversation, user verbosity, etc.) and turn-by-turn coordination. We also suggest a test to identify whether stylistic coordination persists even after accounting for length coordination and contextual factors. PMID:26115446

Longitudinal changes in everyday life after home modifications for people aging with disabilities.

PubMed

Petersson, Ingela; Kottorp, Anders; Bergström, Jakob; Lilja, Margareta

2009-05-01

To investigate longitudinal impacts of home modifications on the difficulty of performing everyday life tasks for people aging with disabilities, and to investigate whether other factors had any additional impacts on difficulty in everyday life tasks for people receiving home modifications. The sample consisted of 103 persons aging with disabilities and in need of home modifications, divided into an intervention group and a comparison group. The data were first subjected to Rasch analysis and a random coefficient model was used. Participants in the intervention group reported a significantly lower level of difficulty in everyday life tasks compared with those in the comparison group. One confounding factor, number of months waiting for home modification, had an impact on difficulty in everyday life. Home modifications are effective in decreasing difficulty in performing everyday life tasks up to six months after the installation. Furthermore, to be effective home modifications need to be installed in a timely fashion. For each consecutive month the person waited for their home modification the difficulty of performing everyday life tasks increased. Therefore, it is important that home modifications be installed as soon as possible after the need has been identified.

Examining the role of unmeasured confounding in mediation analysis with genetic and genomic applications.

PubMed

Lutz, Sharon M; Thwing, Annie; Schmiege, Sarah; Kroehl, Miranda; Baker, Christopher D; Starling, Anne P; Hokanson, John E; Ghosh, Debashis

2017-07-19

In mediation analysis if unmeasured confounding is present, the estimates for the direct and mediated effects may be over or under estimated. Most methods for the sensitivity analysis of unmeasured confounding in mediation have focused on the mediator-outcome relationship. The Umediation R package enables the user to simulate unmeasured confounding of the exposure-mediator, exposure-outcome, and mediator-outcome relationships in order to see how the results of the mediation analysis would change in the presence of unmeasured confounding. We apply the Umediation package to the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) study to examine the role of unmeasured confounding due to population stratification on the effect of a single nucleotide polymorphism (SNP) in the CHRNA5/3/B4 locus on pulmonary function decline as mediated by cigarette smoking. Umediation is a flexible R package that examines the role of unmeasured confounding in mediation analysis allowing for normally distributed or Bernoulli distributed exposures, outcomes, mediators, measured confounders, and unmeasured confounders. Umediation also accommodates multiple measured confounders, multiple unmeasured confounders, and allows for a mediator-exposure interaction on the outcome. Umediation is available as an R package at https://github.com/SharonLutz/Umediation A tutorial on how to install and use the Umediation package is available in the Additional file 1.

Confounding in statistical mediation analysis: What it is and how to address it.

PubMed

Valente, Matthew J; Pelham, William E; Smyth, Heather; MacKinnon, David P

2017-11-01

Psychology researchers are often interested in mechanisms underlying how randomized interventions affect outcomes such as substance use and mental health. Mediation analysis is a common statistical method for investigating psychological mechanisms that has benefited from exciting new methodological improvements over the last 2 decades. One of the most important new developments is methodology for estimating causal mediated effects using the potential outcomes framework for causal inference. Potential outcomes-based methods developed in epidemiology and statistics have important implications for understanding psychological mechanisms. We aim to provide a concise introduction to and illustration of these new methods and emphasize the importance of confounder adjustment. First, we review the traditional regression approach for estimating mediated effects. Second, we describe the potential outcomes framework. Third, we define what a confounder is and how the presence of a confounder can provide misleading evidence regarding mechanisms of interventions. Fourth, we describe experimental designs that can help rule out confounder bias. Fifth, we describe new statistical approaches to adjust for measured confounders of the mediator-outcome relation and sensitivity analyses to probe effects of unmeasured confounders on the mediated effect. All approaches are illustrated with application to a real counseling intervention dataset. Counseling psychologists interested in understanding the causal mechanisms of their interventions can benefit from incorporating the most up-to-date techniques into their mediation analyses. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Cardiovascular health, traffic-related air pollution and noise: are associations mutually confounded? A systematic review.

PubMed

Tétreault, Louis-François; Perron, Stéphane; Smargiassi, Audrey

2013-10-01

This review assessed the confounding effect of one traffic-related exposure (noise or air pollutants) on the association between the other exposure and cardiovascular outcomes. A systematic review was conducted with the databases Medline and Embase. The confounding effects in studies were assessed by using change in the estimate with a 10 % cutoff point. The influence on the change in the estimate of the quality of the studies, the exposure assessment methods and the correlation between road noise and air pollutions were also assessed. Nine publications were identified. For most studies, the specified confounders produced changes in estimates <10 %. The correlation between noise and pollutants, the quality of the study and of the exposure assessment do not seem to influence the confounding effects. Results from this review suggest that confounding of cardiovascular effects by noise or air pollutants is low, though with further improvements in exposure assessment, the situation may change. More studies using pollution indicators specific to road traffic are needed to properly assess if noise and air pollution are subjected to confounding.

Confronting ‘confounding by health system use’ in Medicare Part D: Comparative effectiveness of propensity score approaches to confounding adjustment

PubMed Central

Polinski, Jennifer M.; Schneeweiss, Sebastian; Glynn, Robert J.; Lii, Joyce; Rassen, Jeremy

2012-01-01

Purpose Under Medicare Part D, patient characteristics influence plan choice, which in turn influences Part D coverage gap entry. We compared pre-defined propensity score (PS) and high-dimensional propensity score (hdPS) approaches to address such ‘confounding by health system use’ in assessing whether coverage gap entry is associated with cardiovascular events or death. Methods We followed 243,079 Medicare patients aged 65+ with linked prescription, medical, and plan-specific data in 2005–2007. Patients reached the coverage gap and were followed until an event or year’s end. Exposed patients were responsible for drug costs in the gap; unexposed patients (patients with non-Part D drug insurance and Part D patients receiving a low-income subsidy (LIS)) received financial assistance. Exposed patients were 1:1 PS- or hdPS-matched to unexposed patients. The PS model included 52 predefined covariates; the hdPS model added 400 empirically identified covariates. Hazard ratios for death and any of five cardiovascular outcomes were compared. In sensitivity analyses, we explored residual confounding using only LIS patients in the unexposed group. Results In unadjusted analyses, exposed patients had no greater hazard of death (HR=1.00; 95% CI, 0.84–1.20) or other outcomes. PS- (HR=1.29;0.99–1.66) and hdPS- (HR=1.11;0.86–1.42) matched analyses showed elevated but non-significant hazards of death. In sensitivity analyses, the PS analysis showed a protective effect (HR=0.78;0.61–0.98), while the hdPS analysis (HR=1.06;0.82–1.37) confirmed the main hdPS findings. Conclusion Although the PS-matched analysis suggested elevated though non-significant hazards of death among patients with no financial assistance during the gap, the hdPS analysis produced lower estimates that were stable across sensitivity analyses. PMID:22552984

Single-Nucleosome Mapping of Histone Modifications in S. cerevisiae

PubMed Central

Kim, Minkyu; Buratowski, Stephen; Schreiber, Stuart L; Friedman, Nir

2005-01-01

Covalent modification of histone proteins plays a role in virtually every process on eukaryotic DNA, from transcription to DNA repair. Many different residues can be covalently modified, and it has been suggested that these modifications occur in a great number of independent, meaningful combinations. Published low-resolution microarray studies on the combinatorial complexity of histone modification patterns suffer from confounding effects caused by the averaging of modification levels over multiple nucleosomes. To overcome this problem, we used a high-resolution tiled microarray with single-nucleosome resolution to investigate the occurrence of combinations of 12 histone modifications on thousands of nucleosomes in actively growing S. cerevisiae. We found that histone modifications do not occur independently; there are roughly two groups of co-occurring modifications. One group of lysine acetylations shows a sharply defined domain of two hypo-acetylated nucleosomes, adjacent to the transcriptional start site, whose occurrence does not correlate with transcription levels. The other group consists of modifications occurring in gradients through the coding regions of genes in a pattern associated with transcription. We found no evidence for a deterministic code of many discrete states, but instead we saw blended, continuous patterns that distinguish nucleosomes at one location (e.g., promoter nucleosomes) from those at another location (e.g., over the 3′ ends of coding regions). These results are consistent with the idea of a simple, redundant histone code, in which multiple modifications share the same role. PMID:16122352

Monoamine oxidase-B (MAO-B) inhibitors: implications for disease-modification in Parkinson’s disease

PubMed Central

2013-01-01

There is a substantial amount of evidence from experimental parkinsonian models to show the neuroprotective effects of monoamine oxidase-B (MAOB) inhibitors. They have been studied for their potential disease-modifying effects in Parkinson’s disease (PD) for over 20 years in various clinical trials. This review provides a summary of the clinical trials and discusses the implications of their results in the context of disease-modification in PD. Earlier clinical trials on selegiline were confounded by symptomatic effects of this drug. Later clinical trials on rasagiline using delayed-start design provide newer insights in disease-modification in PD but success in achieving the aims of this strategy remain elusive due to obstacles, some of which may be insurmountable. PMID:24011391

Wind turbines and idiopathic symptoms: The confounding effect of concurrent environmental exposures.

PubMed

Blanes-Vidal, Victoria; Schwartz, Joel

2016-01-01

Whether or not wind turbines pose a risk to human health is a matter of heated debate. Personal reactions to other environmental exposures occurring in the same settings as wind turbines may be responsible of the reported symptoms. However, these have not been accounted for in previous studies. We investigated whether there is an association between residential proximity to wind turbines and idiopathic symptoms, after controlling for personal reactions to other environmental co-exposures. We assessed wind turbine exposures in 454 residences as the distance to the closest wind turbine (Dw) and number of wind turbines <1000m (Nw1000). Information on symptoms, demographics and personal reactions to exposures was obtained by a blind questionnaire. We identified confounders using confounders' selection criteria and used adjusted logistic regression models to estimate associations. When controlling only for socio-demographic characteristics, log10Dw was associated with "unnatural fatigue" (ORadj=0.38, 95%CI=0.15-1.00) and "difficulty concentrating" (ORadj=0.26, 95%CI=0.08-0.83) and Nw1000 was associated with "unnatural fatigue" (ORadj=1.35, 95%CI=1.07-1.70) and "headache" (ORadj=1.26, 95%CI=1.00-1.58). After controlling for personal reactions to noise from sources different from wind turbines and agricultural odor exposure, we did not observe a significant relationship between residential proximity to wind turbines and symptoms and the parameter estimates were attenuated toward zero. Wind turbines-health associations can be confounded by personal reactions to other environmental co-exposures. Isolated associations reported in the literature may be due to confounding bias. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessing Sensitivity to Unmeasured Confounding Using a Simulated Potential Confounder

ERIC Educational Resources Information Center

Carnegie, Nicole Bohme; Harada, Masataka; Hill, Jennifer L.

2016-01-01

A major obstacle to developing evidenced-based policy is the difficulty of implementing randomized experiments to answer all causal questions of interest. When using a nonexperimental study, it is critical to assess how much the results could be affected by unmeasured confounding. We present a set of graphical and numeric tools to explore the…

Confounding and Statistical Significance of Indirect Effects: Childhood Adversity, Education, Smoking, and Anxious and Depressive Symptomatology.

PubMed

Sheikh, Mashhood Ahmed

2017-01-01

The life course perspective, the risky families model, and stress-and-coping models provide the rationale for assessing the role of smoking as a mediator in the association between childhood adversity and anxious and depressive symptomatology (ADS) in adulthood. However, no previous study has assessed the independent mediating role of smoking in the association between childhood adversity and ADS in adulthood. Moreover, the importance of mediator-response confounding variables has rarely been demonstrated empirically in social and psychiatric epidemiology. The aim of this paper was to (i) assess the mediating role of smoking in adulthood in the association between childhood adversity and ADS in adulthood, and (ii) assess the change in estimates due to different mediator-response confounding factors (education, alcohol intake, and social support). The present analysis used data collected from 1994 to 2008 within the framework of the Tromsø Study ( N = 4,530), a representative prospective cohort study of men and women. Seven childhood adversities (low mother's education, low father's education, low financial conditions, exposure to passive smoke, psychological abuse, physical abuse, and substance abuse distress) were used to create a childhood adversity score. Smoking status was measured at a mean age of 54.7 years (Tromsø IV), and ADS in adulthood was measured at a mean age of 61.7 years (Tromsø V). Mediation analysis was used to assess the indirect effect and the proportion of mediated effect (%) of childhood adversity on ADS in adulthood via smoking in adulthood. The test-retest reliability of smoking was good (Kappa: 0.67, 95% CI: 0.63; 0.71) in this sample. Childhood adversity was associated with a 10% increased risk of smoking in adulthood (Relative risk: 1.10, 95% CI: 1.03; 1.18), and both childhood adversity and smoking in adulthood were associated with greater levels of ADS in adulthood ( p < 0.001). Smoking in adulthood did not significantly mediate the

Confounding and Statistical Significance of Indirect Effects: Childhood Adversity, Education, Smoking, and Anxious and Depressive Symptomatology

PubMed Central

Sheikh, Mashhood Ahmed

2017-01-01

The life course perspective, the risky families model, and stress-and-coping models provide the rationale for assessing the role of smoking as a mediator in the association between childhood adversity and anxious and depressive symptomatology (ADS) in adulthood. However, no previous study has assessed the independent mediating role of smoking in the association between childhood adversity and ADS in adulthood. Moreover, the importance of mediator-response confounding variables has rarely been demonstrated empirically in social and psychiatric epidemiology. The aim of this paper was to (i) assess the mediating role of smoking in adulthood in the association between childhood adversity and ADS in adulthood, and (ii) assess the change in estimates due to different mediator-response confounding factors (education, alcohol intake, and social support). The present analysis used data collected from 1994 to 2008 within the framework of the Tromsø Study (N = 4,530), a representative prospective cohort study of men and women. Seven childhood adversities (low mother's education, low father's education, low financial conditions, exposure to passive smoke, psychological abuse, physical abuse, and substance abuse distress) were used to create a childhood adversity score. Smoking status was measured at a mean age of 54.7 years (Tromsø IV), and ADS in adulthood was measured at a mean age of 61.7 years (Tromsø V). Mediation analysis was used to assess the indirect effect and the proportion of mediated effect (%) of childhood adversity on ADS in adulthood via smoking in adulthood. The test-retest reliability of smoking was good (Kappa: 0.67, 95% CI: 0.63; 0.71) in this sample. Childhood adversity was associated with a 10% increased risk of smoking in adulthood (Relative risk: 1.10, 95% CI: 1.03; 1.18), and both childhood adversity and smoking in adulthood were associated with greater levels of ADS in adulthood (p < 0.001). Smoking in adulthood did not significantly mediate the

Assessing mediation using marginal structural models in the presence of confounding and moderation

PubMed Central

Coffman, Donna L.; Zhong, Wei

2012-01-01

This paper presents marginal structural models (MSMs) with inverse propensity weighting (IPW) for assessing mediation. Generally, individuals are not randomly assigned to levels of the mediator. Therefore, confounders of the mediator and outcome may exist that limit causal inferences, a goal of mediation analysis. Either regression adjustment or IPW can be used to take confounding into account, but IPW has several advantages. Regression adjustment of even one confounder of the mediator and outcome that has been influenced by treatment results in biased estimates of the direct effect (i.e., the effect of treatment on the outcome that does not go through the mediator). One advantage of IPW is that it can properly adjust for this type of confounding, assuming there are no unmeasured confounders. Further, we illustrate that IPW estimation provides unbiased estimates of all effects when there is a baseline moderator variable that interacts with the treatment, when there is a baseline moderator variable that interacts with the mediator, and when the treatment interacts with the mediator. IPW estimation also provides unbiased estimates of all effects in the presence of non-randomized treatments. In addition, for testing mediation we propose a test of the null hypothesis of no mediation. Finally, we illustrate this approach with an empirical data set in which the mediator is continuous, as is often the case in psychological research. PMID:22905648

On the Confounding Effect of Temperature on Chemical Shift-Encoded Fat Quantification

PubMed Central

Hernando, Diego; Sharma, Samir D.; Kramer, Harald; Reeder, Scott B.

2014-01-01

Purpose To characterize the confounding effect of temperature on chemical shift-encoded (CSE) fat quantification. Methods The proton resonance frequency of water, unlike triglycerides, depends on temperature. This leads to a temperature dependence of the spectral models of fat (relative to water) that are commonly used by CSE-MRI methods. Simulation analysis was performed for 1.5 Tesla CSE fat–water signals at various temperatures and echo time combinations. Oil–water phantoms were constructed and scanned at temperatures between 0 and 40°C using spectroscopy and CSE imaging at three echo time combinations. An explanted human liver, rejected for transplantation due to steatosis, was scanned using spectroscopy and CSE imaging. Fat–water reconstructions were performed using four different techniques: magnitude and complex fitting, with standard or temperature-corrected signal modeling. Results In all experiments, magnitude fitting with standard signal modeling resulted in large fat quantification errors. Errors were largest for echo time combinations near TEinit ≈ 1.3 ms, ΔTE ≈ 2.2 ms. Errors in fat quantification caused by temperature-related frequency shifts were smaller with complex fitting, and were avoided using a temperature-corrected signal model. Conclusion Temperature is a confounding factor for fat quantification. If not accounted for, it can result in large errors in fat quantifications in phantom and ex vivo acquisitions. PMID:24123362

Task-independent effects are potential confounders in longitudinal imaging studies of learning in schizophrenia.

PubMed

Korostil, Michele; Fatima, Zainab; Kovacevic, Natasha; Menon, Mahesh; McIntosh, Anthony Randal

2016-01-01

Learning impairment is a core deficit in schizophrenia that impacts on real-world functioning and yet, elucidating its underlying neural basis remains a challenge. A key issue when interpreting learning-task experiments is that task-independent changes may confound interpretation of task-related signal changes in neuroimaging studies. The nature of these task-independent changes in schizophrenia is unknown. Therefore, we examined task-independent "time effects" in a group of participants with schizophrenia contrasted with healthy participants in a longitudinal fMRI learning-experiment designed to allow for examination of non-specific effects of time. Flanking the learning portions of the experiment with a task-of-no-interest allowed us to extract task-independent BOLD changes. Task-independent effects occurred in both groups, but were more robust in the schizophrenia group. There was a significant interaction effect between group and time in a distributed activity pattern that included inferior and superior temporal regions, frontal areas (left anterior insula and superior medial gyri), and parietal areas (posterior cingulate cortices and precuneus). This pattern showed task-independent linear decrease in BOLD amplitude over the two scanning sessions for the schizophrenia group, but showed either opposite effect or no activity changes for the control group. There was a trend towards a correlation between task-independent effects and the presence of more negative symptoms in the schizophrenia group. The strong interaction between group and time suggests that both the scanning experience as a whole and the transition between task-types evokes a different response in persons with schizophrenia and may confound interpretation of learning-related longitudinal imaging experiments if not explicitly considered.

Correction of confounding bias in non-randomized studies by appropriate weighting.

PubMed

Schmoor, Claudia; Gall, Christine; Stampf, Susanne; Graf, Erika

2011-03-01

In non-randomized studies, the assessment of a causal effect of treatment or exposure on outcome is hampered by possible confounding. Applying multiple regression models including the effects of treatment and covariates on outcome is the well-known classical approach to adjust for confounding. In recent years other approaches have been promoted. One of them is based on the propensity score and considers the effect of possible confounders on treatment as a relevant criterion for adjustment. Another proposal is based on using an instrumental variable. Here inference relies on a factor, the instrument, which affects treatment but is thought to be otherwise unrelated to outcome, so that it mimics randomization. Each of these approaches can basically be interpreted as a simple reweighting scheme, designed to address confounding. The procedures will be compared with respect to their fundamental properties, namely, which bias they aim to eliminate, which effect they aim to estimate, and which parameter is modelled. We will expand our overview of methods for analysis of non-randomized studies to methods for analysis of randomized controlled trials and show that analyses of both study types may target different effects and different parameters. The considerations will be illustrated using a breast cancer study with a so-called Comprehensive Cohort Study design, including a randomized controlled trial and a non-randomized study in the same patient population as sub-cohorts. This design offers ideal opportunities to discuss and illustrate the properties of the different approaches. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mismeasurement and the resonance of strong confounders: correlated errors.

PubMed

Marshall, J R; Hastrup, J L; Ross, J S

1999-07-01

Confounding in epidemiology, and the limits of standard methods of control for an imperfectly measured confounder, have been understood for some time. However, most treatments of this problem are based on the assumption that errors of measurement in confounding and confounded variables are independent. This paper considers the situation in which a strong risk factor (confounder) and an inconsequential but suspected risk factor (confounded) are each measured with errors that are correlated; the situation appears especially likely to occur in the field of nutritional epidemiology. Error correlation appears to add little to measurement error as a source of bias in estimating the impact of a strong risk factor: it can add to, diminish, or reverse the bias induced by measurement error in estimating the impact of the inconsequential risk factor. Correlation of measurement errors can add to the difficulty involved in evaluating structures in which confounding and measurement error are present. In its presence, observed correlations among risk factors can be greater than, less than, or even opposite to the true correlations. Interpretation of multivariate epidemiologic structures in which confounding is likely requires evaluation of measurement error structures, including correlations among measurement errors.

Using instrumental variables to estimate a Cox's proportional hazards regression subject to additive confounding

PubMed Central

Tosteson, Tor D.; Morden, Nancy E.; Stukel, Therese A.; O'Malley, A. James

2014-01-01

The estimation of treatment effects is one of the primary goals of statistics in medicine. Estimation based on observational studies is subject to confounding. Statistical methods for controlling bias due to confounding include regression adjustment, propensity scores and inverse probability weighted estimators. These methods require that all confounders are recorded in the data. The method of instrumental variables (IVs) can eliminate bias in observational studies even in the absence of information on confounders. We propose a method for integrating IVs within the framework of Cox's proportional hazards model and demonstrate the conditions under which it recovers the causal effect of treatment. The methodology is based on the approximate orthogonality of an instrument with unobserved confounders among those at risk. We derive an estimator as the solution to an estimating equation that resembles the score equation of the partial likelihood in much the same way as the traditional IV estimator resembles the normal equations. To justify this IV estimator for a Cox model we perform simulations to evaluate its operating characteristics. Finally, we apply the estimator to an observational study of the effect of coronary catheterization on survival. PMID:25506259

Using instrumental variables to estimate a Cox's proportional hazards regression subject to additive confounding.

PubMed

MacKenzie, Todd A; Tosteson, Tor D; Morden, Nancy E; Stukel, Therese A; O'Malley, A James

2014-06-01

The estimation of treatment effects is one of the primary goals of statistics in medicine. Estimation based on observational studies is subject to confounding. Statistical methods for controlling bias due to confounding include regression adjustment, propensity scores and inverse probability weighted estimators. These methods require that all confounders are recorded in the data. The method of instrumental variables (IVs) can eliminate bias in observational studies even in the absence of information on confounders. We propose a method for integrating IVs within the framework of Cox's proportional hazards model and demonstrate the conditions under which it recovers the causal effect of treatment. The methodology is based on the approximate orthogonality of an instrument with unobserved confounders among those at risk. We derive an estimator as the solution to an estimating equation that resembles the score equation of the partial likelihood in much the same way as the traditional IV estimator resembles the normal equations. To justify this IV estimator for a Cox model we perform simulations to evaluate its operating characteristics. Finally, we apply the estimator to an observational study of the effect of coronary catheterization on survival.

Assessing mediation using marginal structural models in the presence of confounding and moderation.

PubMed

Coffman, Donna L; Zhong, Wei

2012-12-01

This article presents marginal structural models with inverse propensity weighting (IPW) for assessing mediation. Generally, individuals are not randomly assigned to levels of the mediator. Therefore, confounders of the mediator and outcome may exist that limit causal inferences, a goal of mediation analysis. Either regression adjustment or IPW can be used to take confounding into account, but IPW has several advantages. Regression adjustment of even one confounder of the mediator and outcome that has been influenced by treatment results in biased estimates of the direct effect (i.e., the effect of treatment on the outcome that does not go through the mediator). One advantage of IPW is that it can properly adjust for this type of confounding, assuming there are no unmeasured confounders. Further, we illustrate that IPW estimation provides unbiased estimates of all effects when there is a baseline moderator variable that interacts with the treatment, when there is a baseline moderator variable that interacts with the mediator, and when the treatment interacts with the mediator. IPW estimation also provides unbiased estimates of all effects in the presence of nonrandomized treatments. In addition, for testing mediation we propose a test of the null hypothesis of no mediation. Finally, we illustrate this approach with an empirical data set in which the mediator is continuous, as is often the case in psychological research. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Task-independent effects are potential confounders in longitudinal imaging studies of learning in schizophrenia

PubMed Central

Korostil, Michele; Fatima, Zainab; Kovacevic, Natasha; Menon, Mahesh; McIntosh, Anthony Randal

2015-01-01

Learning impairment is a core deficit in schizophrenia that impacts on real-world functioning and yet, elucidating its underlying neural basis remains a challenge. A key issue when interpreting learning-task experiments is that task-independent changes may confound interpretation of task-related signal changes in neuroimaging studies. The nature of these task-independent changes in schizophrenia is unknown. Therefore, we examined task-independent “time effects” in a group of participants with schizophrenia contrasted with healthy participants in a longitudinal fMRI learning-experiment designed to allow for examination of non-specific effects of time. Flanking the learning portions of the experiment with a task-of-no-interest allowed us to extract task-independent BOLD changes. Task-independent effects occurred in both groups, but were more robust in the schizophrenia group. There was a significant interaction effect between group and time in a distributed activity pattern that included inferior and superior temporal regions, frontal areas (left anterior insula and superior medial gyri), and parietal areas (posterior cingulate cortices and precuneus). This pattern showed task-independent linear decrease in BOLD amplitude over the two scanning sessions for the schizophrenia group, but showed either opposite effect or no activity changes for the control group. There was a trend towards a correlation between task-independent effects and the presence of more negative symptoms in the schizophrenia group. The strong interaction between group and time suggests that both the scanning experience as a whole and the transition between task-types evokes a different response in persons with schizophrenia and may confound interpretation of learning-related longitudinal imaging experiments if not explicitly considered. PMID:26759790

On Estimation of the Survivor Average Causal Effect in Observational Studies when Important Confounders are Missing Due to Death

PubMed Central

Egleston, Brian L.; Scharfstein, Daniel O.; MacKenzie, Ellen

2008-01-01

We focus on estimation of the causal effect of treatment on the functional status of individuals at a fixed point in time t* after they have experienced a catastrophic event, from observational data with the following features: (1) treatment is imposed shortly after the event and is non-randomized, (2) individuals who survive to t* are scheduled to be interviewed, (3) there is interview non-response, (4) individuals who die prior to t* are missing information on pre-event confounders, (5) medical records are abstracted on all individuals to obtain information on post-event, pre-treatment confounding factors. To address the issue of survivor bias, we seek to estimate the survivor average causal effect (SACE), the effect of treatment on functional status among the cohort of individuals who would survive to t* regardless of whether or not assigned to treatment. To estimate this effect from observational data, we need to impose untestable assumptions, which depend on the collection of all confounding factors. Since pre-event information is missing on those who die prior to t*, it is unlikely that these data are missing at random (MAR). We introduce a sensitivity analysis methodology to evaluate the robustness of SACE inferences to deviations from the MAR assumption. We apply our methodology to the evaluation of the effect of trauma center care on vitality outcomes using data from the National Study on Costs and Outcomes of Trauma Care. PMID:18759833

The alarming problems of confounding equivalence using logistic regression models in the perspective of causal diagrams.

PubMed

Yu, Yuanyuan; Li, Hongkai; Sun, Xiaoru; Su, Ping; Wang, Tingting; Liu, Yi; Yuan, Zhongshang; Liu, Yanxun; Xue, Fuzhong

2017-12-28

Confounders can produce spurious associations between exposure and outcome in observational studies. For majority of epidemiologists, adjusting for confounders using logistic regression model is their habitual method, though it has some problems in accuracy and precision. It is, therefore, important to highlight the problems of logistic regression and search the alternative method. Four causal diagram models were defined to summarize confounding equivalence. Both theoretical proofs and simulation studies were performed to verify whether conditioning on different confounding equivalence sets had the same bias-reducing potential and then to select the optimum adjusting strategy, in which logistic regression model and inverse probability weighting based marginal structural model (IPW-based-MSM) were compared. The "do-calculus" was used to calculate the true causal effect of exposure on outcome, then the bias and standard error were used to evaluate the performances of different strategies. Adjusting for different sets of confounding equivalence, as judged by identical Markov boundaries, produced different bias-reducing potential in the logistic regression model. For the sets satisfied G-admissibility, adjusting for the set including all the confounders reduced the equivalent bias to the one containing the parent nodes of the outcome, while the bias after adjusting for the parent nodes of exposure was not equivalent to them. In addition, all causal effect estimations through logistic regression were biased, although the estimation after adjusting for the parent nodes of exposure was nearest to the true causal effect. However, conditioning on different confounding equivalence sets had the same bias-reducing potential under IPW-based-MSM. Compared with logistic regression, the IPW-based-MSM could obtain unbiased causal effect estimation when the adjusted confounders satisfied G-admissibility and the optimal strategy was to adjust for the parent nodes of outcome, which

Negative affectivity: moderator or confound in emotional dissonance-outcome relationships?

PubMed

Abraham, R

1999-01-01

This study was an examination of the impact of negative affectivity on relationships between emotional dissonance, job satisfaction, and emotional exhaustion. Negative affectivity is the predisposition to view life in negative terms. Emotional dissonance originates from the conflict between expressed and experienced emotions. In organizations that require the expression of positive emotions, high negative affectivity individuals may experience conflict between expressed, positive emotions and felt, negative emotions. A moderator effect exists when high negative affectivity individuals experience greater job dissatisfaction and emotional exhaustion. Alternatively, negative affectivity may exert a confounding effect through its relationship to both emotional dissonance and its outcomes. Empirical tests showed that negative affectivity moderated the emotional dissonance-job satisfaction relationship and confounded the emotional dissonance-emotional exhaustion relationship.

Diagnostics for Confounding of Time-varying and Other Joint Exposures.

PubMed

Jackson, John W

2016-11-01

The effects of joint exposures (or exposure regimes) include those of adhering to assigned treatment versus placebo in a randomized controlled trial, duration of exposure in a cohort study, interactions between exposures, and direct effects of exposure, among others. Unlike the setting of a single point exposure (e.g., propensity score matching), there are few tools to describe confounding for joint exposures or how well a method resolves it. Investigators need tools that describe confounding in ways that are conceptually grounded and intuitive for those who read, review, and use applied research to guide policy. We revisit the implications of exchangeability conditions that hold in sequentially randomized trials, and the bias structure that motivates the use of g-methods, such as marginal structural models. From these, we develop covariate balance diagnostics for joint exposures that can (1) describe time-varying confounding, (2) assess whether covariates are predicted by prior exposures given their past, the indication for g-methods, and (3) describe residual confounding after inverse probability weighting. For each diagnostic, we present time-specific metrics that encompass a wide class of joint exposures, including regimes of multivariate time-varying exposures in censored data, with multivariate point exposures as a special case. We outline how to estimate these directly or with regression and how to average them over person-time. Using a simulated example, we show how these metrics can be presented graphically. This conceptually grounded framework can potentially aid the transparent design, analysis, and reporting of studies that examine joint exposures. We provide easy-to-use tools to implement it.

On P values and effect modification.

PubMed

Mayer, Martin

2017-12-01

A crucial element of evidence-based healthcare is the sound understanding and use of statistics. As part of instilling sound statistical knowledge and practice, it seems useful to highlight instances of unsound statistical reasoning or practice, not merely in captious or vitriolic spirit, but rather, to use such error as a springboard for edification by giving tangibility to the concepts at hand and highlighting the importance of avoiding such error. This article aims to provide an instructive overview of two key statistical concepts: effect modification and P values. A recent article published in the Journal of the American College of Cardiology on side effects related to statin therapy offers a notable example of errors in understanding effect modification and P values, and although not so critical as to entirely invalidate the article, the errors still demand considerable scrutiny and correction. In doing so, this article serves as an instructive overview of the statistical concepts of effect modification and P values. Judicious handling of statistics is imperative to avoid muddying their utility. This article contributes to the body of literature aiming to improve the use of statistics, which in turn will help facilitate evidence appraisal, synthesis, translation, and application.

"A Bayesian sensitivity analysis to evaluate the impact of unmeasured confounding with external data: a real world comparative effectiveness study in osteoporosis".

PubMed

Zhang, Xiang; Faries, Douglas E; Boytsov, Natalie; Stamey, James D; Seaman, John W

2016-09-01

Observational studies are frequently used to assess the effectiveness of medical interventions in routine clinical practice. However, the use of observational data for comparative effectiveness is challenged by selection bias and the potential of unmeasured confounding. This is especially problematic for analyses using a health care administrative database, in which key clinical measures are often not available. This paper provides an approach to conducting a sensitivity analyses to investigate the impact of unmeasured confounding in observational studies. In a real world osteoporosis comparative effectiveness study, the bone mineral density (BMD) score, an important predictor of fracture risk and a factor in the selection of osteoporosis treatments, is unavailable in the data base and lack of baseline BMD could potentially lead to significant selection bias. We implemented Bayesian twin-regression models, which simultaneously model both the observed outcome and the unobserved unmeasured confounder, using information from external sources. A sensitivity analysis was also conducted to assess the robustness of our conclusions to changes in such external data. The use of Bayesian modeling in this study suggests that the lack of baseline BMD did have a strong impact on the analysis, reversing the direction of the estimated effect (odds ratio of fracture incidence at 24 months: 0.40 vs. 1.36, with/without adjusting for unmeasured baseline BMD). The Bayesian twin-regression models provide a flexible sensitivity analysis tool to quantitatively assess the impact of unmeasured confounding in observational studies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of site-specific modification on restriction endonucleases and DNA modification methyltransferases.

PubMed Central

McClelland, M; Nelson, M; Raschke, E

1994-01-01

Restriction endonucleases have site-specific interactions with DNA that can often be inhibited by site-specific DNA methylation and other site-specific DNA modifications. However, such inhibition cannot generally be predicted. The empirically acquired data on these effects are tabulated for over 320 restriction endonucleases. In addition, a table of known site-specific DNA modification methyltransferases and their specificities is presented along with EMBL database accession numbers for cloned genes. PMID:7937074

Control selection and confounding factors: A lesson from a Japanese case-control study to examine acellular pertussis vaccine effectiveness.

PubMed

Ohfuji, Satoko; Okada, Kenji; Nakano, Takashi; Ito, Hiroaki; Hara, Megumi; Kuroki, Haruo; Hirota, Yoshio

2017-08-24

When using a case-control study design to examine vaccine effectiveness, both the selection of control subjects and the consideration of potential confounders must be the important issues to ensure accurate results. In this report, we described our experience from a case-control study conducted to evaluate the effectiveness of acellular pertussis vaccine combined with diphtheria-tetanus toxoids (DTaP vaccine). Newly diagnosed pertussis cases and age- and sex-matched friend-controls were enrolled, and the history of DTaP vaccination was compared between groups. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for development of pertussis. After adjustment for potential confounders, four doses of DTaP vaccination showed a lower OR for pediatrician-diagnosed pertussis (OR=0.11, 95% CI, 0.01-0.99). In addition, the decreasing OR of four doses vaccination was more pronounced for laboratory-confirmed pertussis (OR=0.07, 95%CI, 0.01-0.82). Besides, positive association with pertussis was observed in subjects with a history of steroid treatment (OR=5.67) and those with a recent contact with a lasting cough (OR=4.12). When using a case-control study to evaluate the effectiveness of vaccines, particularly those for uncommon infectious diseases such as pertussis, the use of friend-controls may be optimal due to the fact that they shared a similar experience for exposure to the pathogen as the cases. In addition, to assess vaccine effectiveness as accurately as possible, the effects of confounding should be adequately controlled with a matching or analysis technique. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Restricted spatial regression in practice: Geostatistical models, confounding, and robustness under model misspecification

USGS Publications Warehouse

Hanks, Ephraim M.; Schliep, Erin M.; Hooten, Mevin B.; Hoeting, Jennifer A.

2015-01-01

In spatial generalized linear mixed models (SGLMMs), covariates that are spatially smooth are often collinear with spatially smooth random effects. This phenomenon is known as spatial confounding and has been studied primarily in the case where the spatial support of the process being studied is discrete (e.g., areal spatial data). In this case, the most common approach suggested is restricted spatial regression (RSR) in which the spatial random effects are constrained to be orthogonal to the fixed effects. We consider spatial confounding and RSR in the geostatistical (continuous spatial support) setting. We show that RSR provides computational benefits relative to the confounded SGLMM, but that Bayesian credible intervals under RSR can be inappropriately narrow under model misspecification. We propose a posterior predictive approach to alleviating this potential problem and discuss the appropriateness of RSR in a variety of situations. We illustrate RSR and SGLMM approaches through simulation studies and an analysis of malaria frequencies in The Gambia, Africa.

A New Method for Partial Correction of Residual Confounding in Time-Series and Other Observational Studies.

PubMed

Flanders, W Dana; Strickland, Matthew J; Klein, Mitchel

2017-05-15

Methods exist to detect residual confounding in epidemiologic studies. One requires a negative control exposure with 2 key properties: 1) conditional independence of the negative control and the outcome (given modeled variables) absent confounding and other model misspecification, and 2) associations of the negative control with uncontrolled confounders and the outcome. We present a new method to partially correct for residual confounding: When confounding is present and our assumptions hold, we argue that estimators from models that include a negative control exposure with these 2 properties tend to be less biased than those from models without it. Using regression theory, we provide theoretical arguments that support our claims. In simulations, we empirically evaluated the approach using a time-series study of ozone effects on asthma emergency department visits. In simulations, effect estimators from models that included the negative control exposure (ozone concentrations 1 day after the emergency department visit) had slightly or modestly less residual confounding than those from models without it. Theory and simulations show that including the negative control can reduce residual confounding, if our assumptions hold. Our method differs from available methods because it uses a regression approach involving an exposure-based indicator rather than a negative control outcome to partially correct for confounding. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Developing hazelnut tissue culture medium free of ion confounding

USDA-ARS?s Scientific Manuscript database

The general approach for tissue culture medium optimization is to use salts as factors in experimental design and analysis. However, using salts as factors leads to ion confounding, making it difficult to detect the effects of individual ions on particular growth responses. This study focused on tes...

Effects of categorization method, regression type, and variable distribution on the inflation of Type-I error rate when categorizing a confounding variable.

PubMed

Barnwell-Ménard, Jean-Louis; Li, Qing; Cohen, Alan A

2015-03-15

The loss of signal associated with categorizing a continuous variable is well known, and previous studies have demonstrated that this can lead to an inflation of Type-I error when the categorized variable is a confounder in a regression analysis estimating the effect of an exposure on an outcome. However, it is not known how the Type-I error may vary under different circumstances, including logistic versus linear regression, different distributions of the confounder, and different categorization methods. Here, we analytically quantified the effect of categorization and then performed a series of 9600 Monte Carlo simulations to estimate the Type-I error inflation associated with categorization of a confounder under different regression scenarios. We show that Type-I error is unacceptably high (>10% in most scenarios and often 100%). The only exception was when the variable categorized was a continuous mixture proxy for a genuinely dichotomous latent variable, where both the continuous proxy and the categorized variable are error-ridden proxies for the dichotomous latent variable. As expected, error inflation was also higher with larger sample size, fewer categories, and stronger associations between the confounder and the exposure or outcome. We provide online tools that can help researchers estimate the potential error inflation and understand how serious a problem this is. Copyright © 2014 John Wiley & Sons, Ltd.

Air pollutants and health outcomes: Assessment of confounding by influenza

NASA Astrophysics Data System (ADS)

Thach, Thuan-Quoc; Wong, Chit-Ming; Chan, King-Pan; Chau, Yuen-Kwan; Neil Thomas, G.; Ou, Chun-Quan; Yang, Lin; Peiris, Joseph S. M.; Lam, Tai-Hing; Hedley, Anthony J.

2010-04-01

We assessed confounding of associations between short-term effects of air pollution and health outcomes by influenza using Hong Kong mortality and hospitalization data for 1996-2002. Three measures of influenza were defined: (i) intensity: weekly proportion of positive influenza viruses, (ii) epidemic: weekly number of positive influenza viruses ≥4% of the annual number for ≥2 consecutive weeks, and (iii) predominance: an epidemic period with co-circulation of respiratory syncytial virus <2% of the annual positive isolates for ≥2 consecutive weeks. We examined effects of influenza on associations between nitrogen dioxide (NO 2), sulfur dioxide (SO 2), particulate matter with aerodynamic diameter ≤10 μm (PM 10) and ozone (O 3) and health outcomes including all natural causes mortality, cardiorespiratory mortality and hospitalization. Generalized additive Poisson regression model with natural cubic splines was fitted to control for time-varying covariates to estimate air pollution health effects. Confounding with influenza was assessed using an absolute difference of >0.1% between unadjusted and adjusted excess risks (ER%). Without adjustment, pollutants were associated with positive ER% for all health outcomes except asthma and stroke hospitalization with SO 2 and stroke hospitalization with O 3. Following adjustment, changes in ER% for all pollutants were <0.1% for all natural causes mortality, but >0.1% for mortality from stroke with NO 2 and SO 2, cardiac or heart disease with NO 2, PM 10 and O 3, lower respiratory infections with NO 2 and O 3 and mortality from chronic obstructive pulmonary disease with all pollutants. Changes >0.1% were seen for acute respiratory disease hospitalization with NO 2, SO 2 and O 3 and acute lower respiratory infections hospitalization with PM 10. Generally, influenza does not confound the observed associations of air pollutants with all natural causes mortality and cardiovascular hospitalization, but for some pollutants

Methods to control for unmeasured confounding in pharmacoepidemiology: an overview.

PubMed

Uddin, Md Jamal; Groenwold, Rolf H H; Ali, Mohammed Sanni; de Boer, Anthonius; Roes, Kit C B; Chowdhury, Muhammad A B; Klungel, Olaf H

2016-06-01

Background Unmeasured confounding is one of the principal problems in pharmacoepidemiologic studies. Several methods have been proposed to detect or control for unmeasured confounding either at the study design phase or the data analysis phase. Aim of the Review To provide an overview of commonly used methods to detect or control for unmeasured confounding and to provide recommendations for proper application in pharmacoepidemiology. Methods/Results Methods to control for unmeasured confounding in the design phase of a study are case only designs (e.g., case-crossover, case-time control, self-controlled case series) and the prior event rate ratio adjustment method. Methods that can be applied in the data analysis phase include, negative control method, perturbation variable method, instrumental variable methods, sensitivity analysis, and ecological analysis. A separate group of methods are those in which additional information on confounders is collected from a substudy. The latter group includes external adjustment, propensity score calibration, two-stage sampling, and multiple imputation. Conclusion As the performance and application of the methods to handle unmeasured confounding may differ across studies and across databases, we stress the importance of using both statistical evidence and substantial clinical knowledge for interpretation of the study results.

A flexible, interpretable framework for assessing sensitivity to unmeasured confounding.

PubMed

Dorie, Vincent; Harada, Masataka; Carnegie, Nicole Bohme; Hill, Jennifer

2016-09-10

When estimating causal effects, unmeasured confounding and model misspecification are both potential sources of bias. We propose a method to simultaneously address both issues in the form of a semi-parametric sensitivity analysis. In particular, our approach incorporates Bayesian Additive Regression Trees into a two-parameter sensitivity analysis strategy that assesses sensitivity of posterior distributions of treatment effects to choices of sensitivity parameters. This results in an easily interpretable framework for testing for the impact of an unmeasured confounder that also limits the number of modeling assumptions. We evaluate our approach in a large-scale simulation setting and with high blood pressure data taken from the Third National Health and Nutrition Examination Survey. The model is implemented as open-source software, integrated into the treatSens package for the R statistical programming language. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Identification of confounders in the assessment of the relationship between lead exposure and child development.

PubMed

Tong, I S; Lu, Y

2001-01-01

To explore the best approach to identify and adjust for confounders in epidemiologic practice. In the Port Pirie cohort study, the selection of covariates was based on both a priori and an empirical consideration. In an assessment of the relationship between exposure to environmental lead and child development, change-in-estimate (CE) and significance testing (ST) criteria were compared in identifying potential confounders. The Pearson correlation coefficients were used to evaluate the potential for collinearity between pairs of major quantitative covariates. In multivariate analyses, the effects of confounding factors were assessed with multiple linear regression models. The nature and number of covariates selected varied with different confounder selection criteria and different cutoffs. Four covariates (i.e., quality of home environment, socioeconomic status (SES), maternal intelligence, and parental smoking behaviour) met the conventional CE criterion (> or =10%), whereas 14 variables met the ST criterion (p < or = 0.25). However, the magnitude of the relationship between blood lead concentration and children's IQ differed slightly after adjustment for confounding, using either the CE (partial regression coefficient: -4.4; 95% confidence interval (CI): -0.5 to -8.3) or ST criterion (-4.3; 95% CI: -0.2 to -8.4). Identification and selection of confounding factors need to be viewed cautiously in epidemiologic studies. Either the CE (e.g., > or = 10%) or ST (e.g., p < or = 0.25) criterion may be implemented in identification of a potential confounder if a study sample is sufficiently large, and both the methods are subject to arbitrariness of selecting a cut-off point. In this study, the CE criterion (i.e., > or = 10%) appears to be more stringent than the ST method (i.e., p < or = 0.25) in the identification of confounders. However, the ST rule cannot be used to determine the trueness of confounding because it cannot reflect the causal relationship between the

Directed acyclic graphs (DAGs): an aid to assess confounding in dental research.

PubMed

Merchant, Anwar T; Pitiphat, Waranuch

2002-12-01

Confounding, a special type of bias, occurs when an extraneous factor is associated with the exposure and independently affects the outcome. In order to get an unbiased estimate of the exposure-outcome relationship, we need to identify potential confounders, collect information on them, design appropriate studies, and adjust for confounding in data analysis. However, it is not always clear which variables to collect information on and adjust for in the analyses. Inappropriate adjustment for confounding can even introduce bias where none existed. Directed acyclic graphs (DAGs) provide a method to select potential confounders and minimize bias in the design and analysis of epidemiological studies. DAGs have been used extensively in expert systems and robotics. Robins (1987) introduced the application of DAGs in epidemiology to overcome shortcomings of traditional methods to control for confounding, especially as they related to unmeasured confounding. DAGs provide a quick and visual way to assess confounding without making parametric assumptions. We introduce DAGs, starting with definitions and rules for basic manipulation, stressing more on applications than theory. We then demonstrate their application in the control of confounding through examples of observational and cross-sectional epidemiological studies.

Resting-state FMRI confounds and cleanup

PubMed Central

Murphy, Kevin; Birn, Rasmus M.; Bandettini, Peter A.

2013-01-01

The goal of resting-state functional magnetic resonance imaging (FMRI) is to investigate the brain’s functional connections by using the temporal similarity between blood oxygenation level dependent (BOLD) signals in different regions of the brain “at rest” as an indicator of synchronous neural activity. Since this measure relies on the temporal correlation of FMRI signal changes between different parts of the brain, any non-neural activity-related process that affects the signals will influence the measure of functional connectivity, yielding spurious results. To understand the sources of these resting-state FMRI confounds, this article describes the origins of the BOLD signal in terms of MR physics and cerebral physiology. Potential confounds arising from motion, cardiac and respiratory cycles, arterial CO2 concentration, blood pressure/cerebral autoregulation, and vasomotion are discussed. Two classes of techniques to remove confounds from resting-state BOLD time series are reviewed: 1) those utilising external recordings of physiology and 2) data-based cleanup methods that only use the resting-state FMRI data itself. Further methods that remove noise from functional connectivity measures at a group level are also discussed. For successful interpretation of resting-state FMRI comparisons and results, noise cleanup is an often over-looked but essential step in the analysis pipeline. PMID:23571418

Effect Modification and Interaction Terms: It Takes Two to Tango.

PubMed

Jupiter, Daniel C

2016-01-01

In this Investigators' Corner I look more deeply into the previously discussed phenomenon of effect modification. I revisit an explanation and examples of the phenomenon and then examine how to account for it statistically. Specifically, I show, in detail, how to write a regression equation that includes interaction terms that account for the effect modification. Finally, I look at interpretation of regression coefficients both with and without the presence of effect modification, and the associated interaction terms. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Interpretational confounding is due to misspecification, not to type of indicator: comment on Howell, Breivik, and Wilcox (2007).

PubMed

Bollen, Kenneth A

2007-06-01

R. D. Howell, E. Breivik, and J. B. Wilcox (2007) have argued that causal (formative) indicators are inherently subject to interpretational confounding. That is, they have argued that using causal (formative) indicators leads the empirical meaning of a latent variable to be other than that assigned to it by a researcher. Their critique of causal (formative) indicators rests on several claims: (a) A latent variable exists apart from the model when there are effect (reflective) indicators but not when there are causal (formative) indicators, (b) causal (formative) indicators need not have the same consequences, (c) causal (formative) indicators are inherently subject to interpretational confounding, and (d) a researcher cannot detect interpretational confounding when using causal (formative) indicators. This article shows that each claim is false. Rather, interpretational confounding is more a problem of structural misspecification of a model combined with an underidentified model that leaves these misspecifications undetected. Interpretational confounding does not occur if the model is correctly specified whether a researcher has causal (formative) or effect (reflective) indicators. It is the validity of a model not the type of indicator that determines the potential for interpretational confounding. Copyright 2007 APA, all rights reserved.

Birth weight and mortality: causality or confounding?

PubMed

Basso, Olga; Wilcox, Allen J; Weinberg, Clarice R

2006-08-15

The association between birth weight and mortality is among the strongest seen in epidemiology. While preterm delivery causes both small babies and high mortality, it does not explain this association. Fetal growth restriction has also been proposed, although its features are unclear because it lacks a definition independent of weight. If, as some postulate, birth weight is not itself on the causal path to mortality, its relation with mortality would have to be explained by confounding factors that decrease birth weight and increase mortality. In this paper, the authors explore the characteristics such confounders would require in order to achieve the observed association between birth weight and mortality. Through a simple simulation, they found that the observed steep gradient of risk for small babies at term can be produced by a rare condition or conditions (with a total prevalence of 0.5%) having profound effects on both fetal growth (-1.7 standard deviations) and mortality (relative risk = 160). Candidate conditions might include malformations, fetal or placental aneuploidy, infections, or imprinting disorders. If such rare factors underlie the association of birth weight with mortality, it would have broad implications for the study of fetal growth restriction and birth weight, and for the prevention of infant mortality.

Instrumental variables as bias amplifiers with general outcome and confounding.

PubMed

Ding, P; VanderWeele, T J; Robins, J M

2017-06-01

Drawing causal inference with observational studies is the central pillar of many disciplines. One sufficient condition for identifying the causal effect is that the treatment-outcome relationship is unconfounded conditional on the observed covariates. It is often believed that the more covariates we condition on, the more plausible this unconfoundedness assumption is. This belief has had a huge impact on practical causal inference, suggesting that we should adjust for all pretreatment covariates. However, when there is unmeasured confounding between the treatment and outcome, estimators adjusting for some pretreatment covariate might have greater bias than estimators without adjusting for this covariate. This kind of covariate is called a bias amplifier, and includes instrumental variables that are independent of the confounder, and affect the outcome only through the treatment. Previously, theoretical results for this phenomenon have been established only for linear models. We fill in this gap in the literature by providing a general theory, showing that this phenomenon happens under a wide class of models satisfying certain monotonicity assumptions. We further show that when the treatment follows an additive or multiplicative model conditional on the instrumental variable and the confounder, these monotonicity assumptions can be interpreted as the signs of the arrows of the causal diagrams.

Alcohol consumption and the risk of type 2 diabetes mellitus: effect modification by hypercholesterolemia: the Third Korea National Health and Nutrition Examination Survey (2005).

PubMed

Jang, Hyeongap; Jang, Won-Mo; Park, Jong-Heon; Oh, Juhwan; Oh, Mu-Kyung; Hwang, Soo-Hee; Kim, Yong-Ik; Lee, Jin-Seok

2012-01-01

While the protective nature of moderate alcohol consumption against diabetes mellitus is well known, inconsistent findings continue to be reported. The possibility of different mixes of effect modifiers has been raised as a reason for those inconsistent findings. Our study aim was to examine potential effect modifiers that can change the effect of alcohol consumption on type 2 diabetes. From data in the third Korea National Health and Nutrition Examination Survey, 3,982 individuals over the age of 30 years who had not been diagnosed with diabetes were selected for inclusion in the study population. Breslow and Day's test and the Wald test between hypercholesterolemia and alcohol consumption in a multiple logistic regression model were used to assess effect modification. Odds ratios for diabetes stratified by alcohol consumption strata and assessed using Breslow and Day's tests for homogeneity indicated that hypercholesterolemia was not a significant confounding factor (p=0.01). However, the Wald test for interaction terms, which is a conservative method of effect modification, was significant (p=0.03). The results indicate that moderate alcohol consumption is not necessarily protective for type 2 diabetes mellitus, if a person has hypercholesterolemia. People who have hypercholesterolemia should be aware of the risk associated with alcohol consumption, a risk that contrasts with the reported protective effect of moderate alcohol consumption on diabetes.

An education gradient in health, a health gradient in education, or a confounded gradient in both?

PubMed

Lynch, Jamie L; von Hippel, Paul T

2016-04-01

There is a positive gradient associating educational attainment with health, yet the explanation for this gradient is not clear. Does higher education improve health (causation)? Do the healthy become highly educated (selection)? Or do good health and high educational attainment both result from advantages established early in the life course (confounding)? This study evaluates these competing explanations by tracking changes in educational attainment and Self-rated Health (SRH) from age 15 to age 31 in the National Longitudinal Study of Youth, 1997 cohort. Ordinal logistic regression confirms that high-SRH adolescents are more likely to become highly educated. This is partly because adolescent SRH is associated with early advantages including adolescents' academic performance, college plans, and family background (confounding); however, net of these confounders adolescent SRH still predicts adult educational attainment (selection). Fixed-effects longitudinal regression shows that educational attainment has little causal effect on SRH at age 31. Completion of a high school diploma or associate's degree has no effect on SRH, while completion of a bachelor's or graduate degree have effects that, though significant, are quite small (less than 0.1 points on a 5-point scale). While it is possible that educational attainment would have greater effect on health at older ages, at age 31 what we see is a health gradient in education, shaped primarily by selection and confounding rather than by a causal effect of education on health. Copyright © 2016 Elsevier Ltd. All rights reserved.

How Confounder Strength Can Affect Allocation of Resources in Electronic Health Records.

PubMed

Lynch, Kristine E; Whitcomb, Brian W; DuVall, Scott L

2018-01-01

When electronic health record (EHR) data are used, multiple approaches may be available for measuring the same variable, introducing potentially confounding factors. While additional information may be gleaned and residual confounding reduced through resource-intensive assessment methods such as natural language processing (NLP), whether the added benefits offset the added cost of the additional resources is not straightforward. We evaluated the implications of misclassification of a confounder when using EHRs. Using a combination of simulations and real data surrounding hospital readmission, we considered smoking as a potential confounder. We compared ICD-9 diagnostic code assignment, which is an easily available measure but has the possibility of substantial misclassification of smoking status, with NLP, a method of determining smoking status that more expensive and time-consuming than ICD-9 code assignment but has less potential for misclassification. Classification of smoking status with NLP consistently produced less residual confounding than the use of ICD-9 codes; however, when minimal confounding was present, differences between the approaches were small. When considerable confounding is present, investing in a superior measurement tool becomes advantageous.

Air pollution and heart rate variability: effect modification by chronic lead exposure.

PubMed

Park, Sung Kyun; O'Neill, Marie S; Vokonas, Pantel S; Sparrow, David; Wright, Robert O; Coull, Brent; Nie, Huiling; Hu, Howard; Schwartz, Joel

2008-01-01

Outdoor air pollution and lead exposure can disturb cardiac autonomic function, but the effects of both these exposures together have not been studied. We examined whether higher cumulative lead exposures, as measured by bone lead, modified cross-sectional associations between air pollution and heart rate variability among 384 elderly men from the Normative Aging Study. We used linear regression, controlling for clinical, demographic, and environmental covariates. We found graded, significant reductions in both high-frequency and low-frequency powers of heart rate variability in relation to ozone and sulfate across the quartiles of tibia lead. Interquartile range increases in ozone and sulfate were associated respectively, with 38% decrease (95% confidence interval = -54.6% to -14.9%) and 22% decrease (-40.4% to 1.6%) in high frequency, and 38% decrease (-51.9% to -20.4%) and 12% decrease (-28.6% to 9.3%) in low frequency, in the highest quartile of tibia lead after controlling for potential confounders. We observed similar but weaker effect modification by tibia lead adjusted for education and cumulative traffic (residuals of the regression of tibia lead on education and cumulative traffic). Patella lead modified only the ozone effect on heart rate variability. People with long-term exposure to higher levels of lead may be more sensitive to cardiac autonomic dysfunction on high air pollution days. Efforts to understand how environmental exposures affect the health of an aging population should consider both current levels of pollution and history of lead exposure as susceptibility factors.

Adjusting for the Confounding Effects of Treatment Switching-The BREAK-3 Trial: Dabrafenib Versus Dacarbazine.

PubMed

Latimer, Nicholas R; Abrams, Keith R; Amonkar, Mayur M; Stapelkamp, Ceilidh; Swann, R Suzanne

2015-07-01

Patients with previously untreated BRAF V600E mutation-positive melanoma in BREAK-3 showed a median overall survival (OS) of 18.2 months for dabrafenib versus 15.6 months for dacarbazine (hazard ratio [HR], 0.76; 95% confidence interval, 0.48-1.21). Because patients receiving dacarbazine were allowed to switch to dabrafenib at disease progression, we attempted to adjust for the confounding effects on OS. Rank preserving structural failure time models (RPSFTMs) and the iterative parameter estimation (IPE) algorithm were used. Two analyses, "treatment group" (assumes treatment effect could continue until death) and "on-treatment observed" (assumes treatment effect disappears with discontinuation), were used to test the assumptions around the durability of the treatment effect. A total of 36 of 63 patients (57%) receiving dacarbazine switched to dabrafenib. The adjusted OS HRs ranged from 0.50 to 0.55, depending on the analysis. The RPSFTM and IPE "treatment group" and "on-treatment observed" analyses performed similarly well. RPSFTM and IPE analyses resulted in point estimates for the OS HR that indicate a substantial increase in the treatment effect compared with the unadjusted OS HR of 0.76. The results are uncertain because of the assumptions associated with the adjustment methods. The confidence intervals continued to cross 1.00; thus, the adjusted estimates did not provide statistically significant evidence of a treatment benefit on survival. However, it is clear that a standard intention-to-treat analysis will be confounded in the presence of treatment switching-a reliance on unadjusted analyses could lead to inappropriate practice. Adjustment analyses provide useful additional information on the estimated treatment effects to inform decision making. Treatment switching is common in oncology trials, and the implications of this for the interpretation of the clinical effectiveness and cost-effectiveness of the novel treatment are important to consider. If

Adjusting for the Confounding Effects of Treatment Switching—The BREAK-3 Trial: Dabrafenib Versus Dacarbazine

PubMed Central

Abrams, Keith R.; Amonkar, Mayur M.; Stapelkamp, Ceilidh; Swann, R. Suzanne

2015-01-01

Background. Patients with previously untreated BRAF V600E mutation-positive melanoma in BREAK-3 showed a median overall survival (OS) of 18.2 months for dabrafenib versus 15.6 months for dacarbazine (hazard ratio [HR], 0.76; 95% confidence interval, 0.48–1.21). Because patients receiving dacarbazine were allowed to switch to dabrafenib at disease progression, we attempted to adjust for the confounding effects on OS. Materials and Methods. Rank preserving structural failure time models (RPSFTMs) and the iterative parameter estimation (IPE) algorithm were used. Two analyses, “treatment group” (assumes treatment effect could continue until death) and “on-treatment observed” (assumes treatment effect disappears with discontinuation), were used to test the assumptions around the durability of the treatment effect. Results. A total of 36 of 63 patients (57%) receiving dacarbazine switched to dabrafenib. The adjusted OS HRs ranged from 0.50 to 0.55, depending on the analysis. The RPSFTM and IPE “treatment group” and “on-treatment observed” analyses performed similarly well. Conclusion. RPSFTM and IPE analyses resulted in point estimates for the OS HR that indicate a substantial increase in the treatment effect compared with the unadjusted OS HR of 0.76. The results are uncertain because of the assumptions associated with the adjustment methods. The confidence intervals continued to cross 1.00; thus, the adjusted estimates did not provide statistically significant evidence of a treatment benefit on survival. However, it is clear that a standard intention-to-treat analysis will be confounded in the presence of treatment switching—a reliance on unadjusted analyses could lead to inappropriate practice. Adjustment analyses provide useful additional information on the estimated treatment effects to inform decision making. Implications for Practice: Treatment switching is common in oncology trials, and the implications of this for the interpretation of the

Combating Unmeasured Confounding in Cross-Sectional Studies: Evaluating Instrumental-Variable and Heckman Selection Models

PubMed Central

DeMaris, Alfred

2014-01-01

Unmeasured confounding is the principal threat to unbiased estimation of treatment “effects” (i.e., regression parameters for binary regressors) in nonexperimental research. It refers to unmeasured characteristics of individuals that lead them both to be in a particular “treatment” category and to register higher or lower values than others on a response variable. In this article, I introduce readers to 2 econometric techniques designed to control the problem, with a particular emphasis on the Heckman selection model (HSM). Both techniques can be used with only cross-sectional data. Using a Monte Carlo experiment, I compare the performance of instrumental-variable regression (IVR) and HSM to that of ordinary least squares (OLS) under conditions with treatment and unmeasured confounding both present and absent. I find HSM generally to outperform IVR with respect to mean-square-error of treatment estimates, as well as power for detecting either a treatment effect or unobserved confounding. However, both HSM and IVR require a large sample to be fully effective. The use of HSM and IVR in tandem with OLS to untangle unobserved confounding bias in cross-sectional data is further demonstrated with an empirical application. Using data from the 2006–2010 General Social Survey (National Opinion Research Center, 2014), I examine the association between being married and subjective well-being. PMID:25110904

LuxGLM: a probabilistic covariate model for quantification of DNA methylation modifications with complex experimental designs

PubMed Central

Äijö, Tarmo; Yue, Xiaojing; Rao, Anjana; Lähdesmäki, Harri

2016-01-01

Motivation: 5-methylcytosine (5mC) is a widely studied epigenetic modification of DNA. The ten-eleven translocation (TET) dioxygenases oxidize 5mC into oxidized methylcytosines (oxi-mCs): 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). DNA methylation modifications have multiple functions. For example, 5mC is shown to be associated with diseases and oxi-mC species are reported to have a role in active DNA demethylation through 5mC oxidation and DNA repair, among others, but the detailed mechanisms are poorly understood. Bisulphite sequencing and its various derivatives can be used to gain information about all methylation modifications at single nucleotide resolution. Analysis of bisulphite based sequencing data is complicated due to the convoluted read-outs and experiment-specific variation in biochemistry. Moreover, statistical analysis is often complicated by various confounding effects. How to analyse 5mC and oxi-mC data sets with arbitrary and complex experimental designs is an open and important problem. Results: We propose the first method to quantify oxi-mC species with arbitrary covariate structures from bisulphite based sequencing data. Our probabilistic modeling framework combines a previously proposed hierarchical generative model for oxi-mC-seq data and a general linear model component to account for confounding effects. We show that our method provides accurate methylation level estimates and accurate detection of differential methylation when compared with existing methods. Analysis of novel and published data gave insights into to the demethylation of the forkhead box P3 (Foxp3) locus during the induced T regulatory cell differentiation. We also demonstrate how our covariate model accurately predicts methylation levels of the Foxp3 locus. Collectively, LuxGLM method improves the analysis of DNA methylation modifications, particularly for oxi-mC species. Availability and Implementation: An implementation of the

Which Propensity Score Method Best Reduces Confounder Imbalance? An Example From a Retrospective Evaluation of a Childhood Obesity Intervention.

PubMed

Schroeder, Krista; Jia, Haomiao; Smaldone, Arlene

Propensity score (PS) methods are increasingly being employed by researchers to reduce bias arising from confounder imbalance when using observational data to examine intervention effects. The purpose of this study was to examine PS theory and methodology and compare application of three PS methods (matching, stratification, weighting) to determine which best improves confounder balance. Baseline characteristics of a sample of 20,518 school-aged children with severe obesity (of whom 1,054 received an obesity intervention) were assessed prior to PS application. Three PS methods were then applied to the data to determine which showed the greatest improvement in confounder balance between the intervention and control group. The effect of each PS method on the outcome variable-body mass index percentile change at one year-was also examined. SAS 9.4 and Comprehensive Meta-analysis statistical software were used for analyses. Prior to PS adjustment, the intervention and control groups differed significantly on seven of 11 potential confounders. PS matching removed all differences. PS stratification and weighting both removed one difference but created two new differences. Sensitivity analyses did not change these results. Body mass index percentile at 1 year decreased in both groups. The size of the decrease was smaller in the intervention group, and the estimate of the decrease varied by PS method. Selection of a PS method should be guided by insight from statistical theory and simulation experiments, in addition to observed improvement in confounder balance. For this data set, PS matching worked best to correct confounder imbalance. Because each method varied in correcting confounder imbalance, we recommend that multiple PS methods be compared for ability to improve confounder balance before implementation in evaluating treatment effects in observational data.

Everything that you have ever been told about assessment center ratings is confounded.

PubMed

Jackson, Duncan J R; Michaelides, George; Dewberry, Chris; Kim, Young-Jae

2016-07-01

Despite a substantial research literature on the influence of dimensions and exercises in assessment centers (ACs), the relative impact of these 2 sources of variance continues to raise uncertainties because of confounding. With confounded effects, it is not possible to establish the degree to which any 1 effect, including those related to exercises and dimensions, influences AC ratings. In the current study (N = 698) we used Bayesian generalizability theory to unconfound all of the possible effects contributing to variance in AC ratings. Our results show that ≤1.11% of the variance in AC ratings was directly attributable to behavioral dimensions, suggesting that dimension-related effects have no practical impact on the reliability of ACs. Even when taking aggregation level into consideration, effects related to general performance and exercises accounted for almost all of the reliable variance in AC ratings. The implications of these findings for recent dimension- and exercise-based perspectives on ACs are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The “Dry-Run” Analysis: A Method for Evaluating Risk Scores for Confounding Control

PubMed Central

Wyss, Richard; Hansen, Ben B.; Ellis, Alan R.; Gagne, Joshua J.; Desai, Rishi J.; Glynn, Robert J.; Stürmer, Til

2017-01-01

Abstract A propensity score (PS) model's ability to control confounding can be assessed by evaluating covariate balance across exposure groups after PS adjustment. The optimal strategy for evaluating a disease risk score (DRS) model's ability to control confounding is less clear. DRS models cannot be evaluated through balance checks within the full population, and they are usually assessed through prediction diagnostics and goodness-of-fit tests. A proposed alternative is the “dry-run” analysis, which divides the unexposed population into “pseudo-exposed” and “pseudo-unexposed” groups so that differences on observed covariates resemble differences between the actual exposed and unexposed populations. With no exposure effect separating the pseudo-exposed and pseudo-unexposed groups, a DRS model is evaluated by its ability to retrieve an unconfounded null estimate after adjustment in this pseudo-population. We used simulations and an empirical example to compare traditional DRS performance metrics with the dry-run validation. In simulations, the dry run often improved assessment of confounding control, compared with the C statistic and goodness-of-fit tests. In the empirical example, PS and DRS matching gave similar results and showed good performance in terms of covariate balance (PS matching) and controlling confounding in the dry-run analysis (DRS matching). The dry-run analysis may prove useful in evaluating confounding control through DRS models. PMID:28338910

Assessing moderated mediation in linear models requires fewer confounding assumptions than assessing mediation.

PubMed

Loeys, Tom; Talloen, Wouter; Goubert, Liesbet; Moerkerke, Beatrijs; Vansteelandt, Stijn

2016-11-01

It is well known from the mediation analysis literature that the identification of direct and indirect effects relies on strong no unmeasured confounding assumptions of no unmeasured confounding. Even in randomized studies the mediator may still be correlated with unobserved prognostic variables that affect the outcome, in which case the mediator's role in the causal process may not be inferred without bias. In the behavioural and social science literature very little attention has been given so far to the causal assumptions required for moderated mediation analysis. In this paper we focus on the index for moderated mediation, which measures by how much the mediated effect is larger or smaller for varying levels of the moderator. We show that in linear models this index can be estimated without bias in the presence of unmeasured common causes of the moderator, mediator and outcome under certain conditions. Importantly, one can thus use the test for moderated mediation to support evidence for mediation under less stringent confounding conditions. We illustrate our findings with data from a randomized experiment assessing the impact of being primed with social deception upon observer responses to others' pain, and from an observational study of individuals who ended a romantic relationship assessing the effect of attachment anxiety during the relationship on mental distress 2 years after the break-up. © 2016 The British Psychological Society.

The impact of confounder selection in propensity scores when applied to prospective cohort studies in pregnancy.

PubMed

Xu, Ronghui; Hou, Jue; Chambers, Christina D

2018-06-01

Our work was motivated by small cohort studies on the risk of birth defects in infants born to pregnant women exposed to medications. We controlled for confounding using propensity scores (PS). The extremely rare events setting renders the matching or stratification infeasible. In addition, the PS itself may be formed via different approaches to select confounders from a relatively long list of potential confounders. We carried out simulation experiments to compare different combinations of approaches: IPW or regression adjustment, with 1) including all potential confounders without selection, 2) selection based on univariate association between the candidate variable and the outcome, 3) selection based on change in effects (CIE). The simulation showed that IPW without selection leads to extremely large variances in the estimated odds ratio, which help to explain the empirical data analysis results that we had observed. Copyright © 2018 Elsevier Inc. All rights reserved.

Controlling for seasonal patterns and time varying confounders in time-series epidemiological models: a simulation study.

PubMed

Perrakis, Konstantinos; Gryparis, Alexandros; Schwartz, Joel; Le Tertre, Alain; Katsouyanni, Klea; Forastiere, Francesco; Stafoggia, Massimo; Samoli, Evangelia

2014-12-10

An important topic when estimating the effect of air pollutants on human health is choosing the best method to control for seasonal patterns and time varying confounders, such as temperature and humidity. Semi-parametric Poisson time-series models include smooth functions of calendar time and weather effects to control for potential confounders. Case-crossover (CC) approaches are considered efficient alternatives that control seasonal confounding by design and allow inclusion of smooth functions of weather confounders through their equivalent Poisson representations. We evaluate both methodological designs with respect to seasonal control and compare spline-based approaches, using natural splines and penalized splines, and two time-stratified CC approaches. For the spline-based methods, we consider fixed degrees of freedom, minimization of the partial autocorrelation function, and general cross-validation as smoothing criteria. Issues of model misspecification with respect to weather confounding are investigated under simulation scenarios, which allow quantifying omitted, misspecified, and irrelevant-variable bias. The simulations are based on fully parametric mechanisms designed to replicate two datasets with different mortality and atmospheric patterns. Overall, minimum partial autocorrelation function approaches provide more stable results for high mortality counts and strong seasonal trends, whereas natural splines with fixed degrees of freedom perform better for low mortality counts and weak seasonal trends followed by the time-season-stratified CC model, which performs equally well in terms of bias but yields higher standard errors. Copyright © 2014 John Wiley & Sons, Ltd.

Disparity modifications and the emotional effects of stereoscopic images

NASA Astrophysics Data System (ADS)

Kawai, Takashi; Atsuta, Daiki; Tomiyama, Yuya; Kim, Sanghyun; Morikawa, Hiroyuki; Mitsuya, Reiko; Häkkinen, Jukka

2014-03-01

This paper describes a study that focuses on disparity changes in emotional scenes of stereoscopic (3D) images, in which an examination of the effects on pleasant and arousal was carried out by adding binocular disparity to 2D images that evoke specific emotions, and applying disparity modification based on the disparity analysis of famous 3D movies. From the results of the experiment, for pleasant, a significant difference was found only for the main effect of the emotions. On the other hand, for arousal, there was a trend of increasing the evaluation values in the order 2D condition, 3D condition and 3D condition applied the disparity modification for happiness, surprise, and fear. This suggests the possibility that binocular disparity and the modification affect arousal.

Can statistic adjustment of OR minimize the potential confounding bias for meta-analysis of case-control study? A secondary data analysis.

PubMed

Liu, Tianyi; Nie, Xiaolu; Wu, Zehao; Zhang, Ying; Feng, Guoshuang; Cai, Siyu; Lv, Yaqi; Peng, Xiaoxia

2017-12-29

Different confounder adjustment strategies were used to estimate odds ratios (ORs) in case-control study, i.e. how many confounders original studies adjusted and what the variables are. This secondary data analysis is aimed to detect whether there are potential biases caused by difference of confounding factor adjustment strategies in case-control study, and whether such bias would impact the summary effect size of meta-analysis. We included all meta-analyses that focused on the association between breast cancer and passive smoking among non-smoking women, as well as each original case-control studies included in these meta-analyses. The relative deviations (RDs) of each original study were calculated to detect how magnitude the adjustment would impact the estimation of ORs, compared with crude ORs. At the same time, a scatter diagram was sketched to describe the distribution of adjusted ORs with different number of adjusted confounders. Substantial inconsistency existed in meta-analysis of case-control studies, which would influence the precision of the summary effect size. First, mixed unadjusted and adjusted ORs were used to combine individual OR in majority of meta-analysis. Second, original studies with different adjustment strategies of confounders were combined, i.e. the number of adjusted confounders and different factors being adjusted in each original study. Third, adjustment did not make the effect size of original studies trend to constringency, which suggested that model fitting might have failed to correct the systematic error caused by confounding. The heterogeneity of confounder adjustment strategies in case-control studies may lead to further bias for summary effect size in meta-analyses, especially for weak or medium associations so that the direction of causal inference would be even reversed. Therefore, further methodological researches are needed, referring to the assessment of confounder adjustment strategies, as well as how to take this kind

Infection with parasitic nematodes confounds vaccination efficacy

PubMed Central

Urban, Joseph F.; Steenhard, Nina R.; Solano-Aguilar, Gloria I.; Dawson, Harry D.; Iweala, Onyinye I.; Nagler, Cathryn R.; Noland, Gregory S.; Kumar, Nirbhay; Anthony, Robert M.; Shea-Donohue, Terez; Weinstock, Joel; Gause, William C.

2007-01-01

T helper (Th) cells produce signature cytokine patterns, induced largely by intracellular versus extracellular pathogens that provide the cellular and molecular basis for counter regulatory expression of protective immunity during concurrent infections. The production of IL-12 and IFN-γ, for example, resulting from exposure to many bacterial, viral, and protozoan pathogens is responsible for Th1-derived protective responses that also can inhibit development of Th2-cells expressing IL-4-dependent immunity to extracellular helminth parasites and vice versa. In a similar manner, concurrent helminth infection alters optimal vaccine-induced responses in humans and livestock; however, the consequences of this condition have not been adequately studied especially in the context of a challenge infection following vaccination. Demands for new and effective vaccines to control chronic and emerging diseases, and the need for rapid deployment of vaccines for bio security concerns requires a systematic evaluation of confounding factors that limit vaccine efficacy. One common albeit overlooked confounder is the presence of gastrointestinal nematode parasites in populations of humans and livestock targeted for vaccination. This is particularly important in areas of the world were helminth infections are prevalent, but the interplay between parasites and emerging diseases that can be transmitted worldwide make this a global issue. In addition, it is not clear if the epidemic in allergic disease in industrialized countries substitutes for geohelminth infection to interfere with effective vaccination regimens. This presentation will focus on recent vaccination studies in mice experimentally infected with Heligmosomoides polygyrus to model the condition of gastrointestinal parasite infestation in mammalian populations targeted for vaccination. In addition, a large animal vaccination and challenge model against Mycoplasma hyopneumonia in swine exposed to Ascaris suum will provide a

Evaluating Public Health Interventions: 3. The Two-Stage Design for Confounding Bias Reduction-Having Your Cake and Eating It Two.

PubMed

Spiegelman, Donna; Rivera-Rodriguez, Claudia L; Haneuse, Sebastien

2016-07-01

In public health evaluations, confounding bias in the estimate of the intervention effect will typically threaten the validity of the findings. It is a common misperception that the only way to avoid this bias is to measure detailed, high-quality data on potential confounders for every intervention participant, but this strategy for adjusting for confounding bias is often infeasible. Rather than ignoring confounding altogether, the two-phase design and analysis-in which detailed high-quality confounding data are obtained among a small subsample-can be considered. We describe the two-stage design and analysis approach, and illustrate its use in the evaluation of an intervention conducted in Dar es Salaam, Tanzania, of an enhanced community health worker program to improve antenatal care uptake.

Microscopic mechanism of amino silicone oil modification and modification effect with different amino group contents based on molecular dynamics simulation

NASA Astrophysics Data System (ADS)

He, Liping; Li, Wenjun; Chen, Dachuan; Yuan, Jianmin; Lu, Gang; Zhou, Dianwu

2018-05-01

The microscopic mechanism of amino silicone oil (ASO) modification of natural fiber was investigated for the first time using molecular dynamics (MD) simulation at the atomic and molecular levels. The MD simulation results indicated that the ASO molecular interacted with the cellulose molecular within the natural fiber, mainly by intermolecular forces of Nsbnd Hsbnd O and Osbnd Hsbnd N hydrogen bonds and the molecular chain of ASO absorbed onto the natural fiber in a selective orientation, i.e., the hydrophobic alkyl groups (sbnd CnH2n+1) project outward and the polar amino groups (sbnd NH2) point to the surface of natural fiber. Consequently, the ASO modification changed the surface characteristic of natural fiber from hydrophilic to hydrophobic. Furthermore, the modification effects of the ASO modification layer with different amino group contents (m:n ratio) were also evaluated in this study by calculating the binding energy between the ASO modifier and natural fiber, and the cohesive energy density and free volume of the ASO modification layer. The results showed that the binding energy reached a maximum when the m:n ratio of ASO was of 8:4, suggesting that a good bonding strength was achieved at this m:n ratio. It was also found that the cohesive energy density enhanced with the increase in the amino group content, and the higher the cohesive energy density, the easier the formation of the ASO modification layer. However, the fraction free volume decreased with the increase in the amino group content. This is good for improving the water-proof property of natural fiber. The present work can provide an effective method for predicting the modification effects and designing the optimized m:n ratio of ASO modification.

Confounding, causality, and confusion: the role of intermediate variables in interpreting observational studies in obstetrics.

PubMed

Ananth, Cande V; Schisterman, Enrique F

2017-08-01

Prospective and retrospective cohorts and case-control studies are some of the most important study designs in epidemiology because, under certain assumptions, they can mimic a randomized trial when done well. These assumptions include, but are not limited to, properly accounting for 2 important sources of bias: confounding and selection bias. While not adjusting the causal association for an intermediate variable will yield an unbiased estimate of the exposure-outcome's total causal effect, it is often that obstetricians will want to adjust for an intermediate variable to assess if the intermediate is the underlying driver of the association. Such a practice must be weighed in light of the underlying research question and whether such an adjustment is necessary should be carefully considered. Gestational age is, by far, the most commonly encountered variable in obstetrics that is often mislabeled as a confounder when, in fact, it may be an intermediate. If, indeed, gestational age is an intermediate but if mistakenly labeled as a confounding variable and consequently adjusted in an analysis, the conclusions can be unexpected. The implications of this overadjustment of an intermediate as though it were a confounder can render an otherwise persuasive study downright meaningless. This commentary provides an exposition of confounding bias, collider stratification, and selection biases, with applications in obstetrics and perinatal epidemiology. Copyright © 2017 Elsevier Inc. All rights reserved.

Weight Loss and Coronary Heart Disease: Sensitivity Analysis for Unmeasured Confounding by Undiagnosed Disease.

PubMed

Danaei, Goodarz; Robins, James M; Young, Jessica G; Hu, Frank B; Manson, JoAnn E; Hernán, Miguel A

2016-03-01

Evidence for the effect of weight loss on coronary heart disease (CHD) or mortality has been mixed. The effect estimates can be confounded due to undiagnosed diseases that may affect weight loss. We used data from the Nurses' Health Study to estimate the 26-year risk of CHD under several hypothetical weight loss strategies. We applied the parametric g-formula and implemented a novel sensitivity analysis for unmeasured confounding due to undiagnosed disease by imposing a lag time for the effect of weight loss on chronic disease. Several sensitivity analyses were conducted. The estimated 26-year risk of CHD did not change under weight loss strategies using lag times from 0 to 18 years. For a 6-year lag time, the risk ratios of CHD for weight loss compared with no weight loss ranged from 1.00 (0.99, 1.02) to 1.02 (0.99, 1.05) for different degrees of weight loss with and without restricting the weight loss strategy to participants with no major chronic disease. Similarly, no protective effect of weight loss was estimated for mortality risk. In contrast, we estimated a protective effect of weight loss on risk of type 2 diabetes. We estimated that maintaining or losing weight after becoming overweight or obese does not reduce the risk of CHD or death in this cohort of middle-age US women. Unmeasured confounding, measurement error, and model misspecification are possible explanations but these did not prevent us from estimating a beneficial effect of weight loss on diabetes.

On negative outcome control of unobserved confounding as a generalization of difference-in-differences

PubMed Central

Sofer, Tamar; Richardson, David B.; Colicino, Elena; Schwartz, Joel; Tchetgen Tchetgen, Eric J.

2016-01-01

The difference-in-differences (DID) approach is a well known strategy for estimating the effect of an exposure in the presence of unobserved confounding. The approach is most commonly used when pre-and post-exposure outcome measurements are available, and one can assume that the association of the unobserved confounder with the outcome is equal in the two exposure groups, and constant over time. Then, one recovers the treatment effect by regressing the change in outcome over time on the exposure. In this paper, we interpret the difference-in-differences as a negative outcome control (NOC) approach. We show that the pre-exposure outcome is a negative control outcome, as it cannot be influenced by the subsequent exposure, and it is affected by both observed and unobserved confounders of the exposure-outcome association of interest. The relation between DID and NOC provides simple conditions under which negative control outcomes can be used to detect and correct for confounding bias. However, for general negative control outcomes, the DID-like assumption may be overly restrictive and rarely credible, because it requires that both the outcome of interest and the control outcome are measured on the same scale. Thus, we present a scale-invariant generalization of the DID that may be used in broader NOC contexts. The proposed approach is demonstrated in simulations and on a Normative Aging Study data set, in which Body Mass Index is used for NOC of the relationship between air pollution and inflammatory outcomes. PMID:28239233

Using expert opinion to quantify unmeasured confounding bias parameters.

PubMed

Navadeh, Soodabeh; Mirzazadeh, Ali; McFarland, Willi; Woolf-King, Sarah; Mansournia, Mohammad Ali

2016-06-27

To develop and apply a method to quantify bias parameters in the case example of the association between alcohol use and HIV-serodiscordant condomless anal sex with potential confounding by sensation seeking among men who have sex with men (MSM), using expert opinion as an external data source. Through an online survey, we sought the input of 41 epidemiologist and behavioural scientists to quantify six parameters in the population of MSM: the proportion of high sensation seeking among heavy-drinking MSM, the proportion of sensation seeking among low-level drinking MSM, and the risk ratio (RR) of the association between sensation seeking and condomless anal sex, for HIV-positive and HIV-negative MSM. Eleven experts responded. For HIV-positive heavy drinkers, the proportion of high sensation seeking was 53.6% (beta distribution [α=5.50, β=4.78]), and 41.1% (beta distribution [α=3.10, β=4.46]) in HIV-negative heavy drinkers. In HIV-positive low-level alcohol drinkers, high sensation seeking was 26.9% (beta distribution [α=1.81, β=4.92]), similar to high sensation seeking among HIV-negative low-level alcohol drinkers (25.3%) (beta distribution [α=2.00, β=5.89]). The lnRR for the association between sensation seeking and condomless anal sex was ln(2.4) (normal distribution [μ=0.889, σ=0.438]) in HIV-positive and ln(1.5) (normal distribution [μ=0.625, σ=0.391]) in HIV-negative MSM. Expert opinion can be a simple and efficient method for deriving bias parameters to quantify and adjust for hypothesized confounding. In this test case, expert opinion confirmed sensation seeking as a confounder for the effect of alcohol on condomless anal sex and provided the parameters necessary for probabilistic bias analysis.

Syphilis may be a confounding factor, not a causative agent, in syphilitic ALS.

PubMed

Tuk, Bert

2016-01-01

Based upon a review of published clinical observations regarding syphilitic amyotrophic lateral sclerosis (ALS), I hypothesize that syphilis is actually a confounding factor, not a causative factor, in syphilitic ALS. Moreover, I propose that the successful treatment of ALS symptoms in patients with syphilitic ALS using penicillin G and hydrocortisone is an indirect consequence of the treatment regimen and is not due to the treatment of syphilis. Specifically, I propose that the observed effect is due to the various pharmacological activities of penicillin G ( e.g ., a GABA receptor antagonist) and/or the multifaceted pharmacological activity of hydrocortisone. The notion that syphilis may be a confounding factor in syphilitic ALS is highly relevant, as it suggests that treating ALS patients with penicillin G and hydrocortisone-regardless of whether they present with syphilitic ALS or non-syphilitic ALS-may be effective at treating this rapidly progressive, highly devastating disease.

Breath biomarkers for lung cancer detection and assessment of smoking related effects--confounding variables, influence of normalization and statistical algorithms.

PubMed

Kischkel, Sabine; Miekisch, Wolfram; Sawacki, Annika; Straker, Eva M; Trefz, Phillip; Amann, Anton; Schubert, Jochen K

2010-11-11

Up to now, none of the breath biomarkers or marker sets proposed for cancer recognition has reached clinical relevance. Possible reasons are the lack of standardized methods of sampling, analysis and data processing and effects of environmental contaminants. Concentration profiles of endogenous and exogenous breath markers were determined in exhaled breath of 31 lung cancer patients, 31 smokers and 31 healthy controls by means of SPME-GC-MS. Different correcting and normalization algorithms and a principal component analysis were applied to the data. Differences of exhalation profiles in cancer and non-cancer patients did not persist if physiology and confounding variables were taken into account. Smoking history, inspired substance concentrations, age and gender were recognized as the most important confounding variables. Normalization onto PCO2 or BSA or correction for inspired concentrations only partially solved the problem. In contrast, previous smoking behaviour could be recognized unequivocally. Exhaled substance concentrations may depend on a variety of parameters other than the disease under investigation. Normalization and correcting parameters have to be chosen with care as compensating effects may be different from one substance to the other. Only well-founded biomarker identification, normalization and data processing will provide clinically relevant information from breath analysis. 2010 Elsevier B.V. All rights reserved.

Confounder Detection in High-Dimensional Linear Models Using First Moments of Spectral Measures.

PubMed

Liu, Furui; Chan, Laiwan

2018-06-12

In this letter, we study the confounder detection problem in the linear model, where the target variable [Formula: see text] is predicted using its [Formula: see text] potential causes [Formula: see text]. Based on an assumption of a rotation-invariant generating process of the model, recent study shows that the spectral measure induced by the regression coefficient vector with respect to the covariance matrix of [Formula: see text] is close to a uniform measure in purely causal cases, but it differs from a uniform measure characteristically in the presence of a scalar confounder. Analyzing spectral measure patterns could help to detect confounding. In this letter, we propose to use the first moment of the spectral measure for confounder detection. We calculate the first moment of the regression vector-induced spectral measure and compare it with the first moment of a uniform spectral measure, both defined with respect to the covariance matrix of [Formula: see text]. The two moments coincide in nonconfounding cases and differ from each other in the presence of confounding. This statistical causal-confounding asymmetry can be used for confounder detection. Without the need to analyze the spectral measure pattern, our method avoids the difficulty of metric choice and multiple parameter optimization. Experiments on synthetic and real data show the performance of this method.

Effect modification by vitamin D receptor genetic polymorphisms in the association between cumulative lead exposure and pulse pressure: a longitudinal study.

PubMed

Jhun, Min A; Hu, Howard; Schwartz, Joel; Weisskopf, Marc G; Nie, Linda H; Sparrow, David; Vokonas, Pantel S; Park, Sung Kyun

2015-01-13

Although the association between lead and cardiovascular disease is well established, potential mechanisms are still poorly understood. Calcium metabolism plays a role in lead toxicity and thus, vitamin D receptor (VDR) polymorphisms have been suggested to modulate the association between lead and health outcomes. We investigated effect modification by VDR genetic polymorphisms in the association between cumulative lead exposure and pulse pressure, a marker of arterial stiffness. We examined 727 participants (3,100 observations from follow-ups from 1991 to 2011) from the Normative Aging Study (NAS), a longitudinal study of aging. Tibia and patella bone lead levels were measured using K-x-ray fluorescence. Four single nucleotide polymorphisms (SNPs) in the VDR gene, Bsm1, Taq1, Apa1, and Fok1, were genotyped. Linear mixed effects models with random intercepts were implemented to take into account repeated measurements. Adjusting for potential confounders, pulse pressure was 2.5 mmHg (95% CI: 0.4-4.7) and 1.9 mmHg (95% CI: 0.1-3.8) greater per interquartile range (IQR) increase in tibia lead (15 μg/g) and patella lead (20 μg/g), respectively, in those with at least one minor frequency allele in Bsm1 compared with those with major frequency allele homozygotes. The observed interaction effect between bone lead and the Bsm1 genotype persists over time during the follow-up. Similar results were observed in effect modification by Taq1. This study suggests that subjects with the minor frequency alleles of VDR Bsm1 or Taq1 may be more susceptible to cumulative lead exposure-related elevated pulse pressure.

On the use and misuse of scalar scores of confounders in design and analysis of observational studies.

PubMed

Pfeiffer, R M; Riedl, R

2015-08-15

We assess the asymptotic bias of estimates of exposure effects conditional on covariates when summary scores of confounders, instead of the confounders themselves, are used to analyze observational data. First, we study regression models for cohort data that are adjusted for summary scores. Second, we derive the asymptotic bias for case-control studies when cases and controls are matched on a summary score, and then analyzed either using conditional logistic regression or by unconditional logistic regression adjusted for the summary score. Two scores, the propensity score (PS) and the disease risk score (DRS) are studied in detail. For cohort analysis, when regression models are adjusted for the PS, the estimated conditional treatment effect is unbiased only for linear models, or at the null for non-linear models. Adjustment of cohort data for DRS yields unbiased estimates only for linear regression; all other estimates of exposure effects are biased. Matching cases and controls on DRS and analyzing them using conditional logistic regression yields unbiased estimates of exposure effect, whereas adjusting for the DRS in unconditional logistic regression yields biased estimates, even under the null hypothesis of no association. Matching cases and controls on the PS yield unbiased estimates only under the null for both conditional and unconditional logistic regression, adjusted for the PS. We study the bias for various confounding scenarios and compare our asymptotic results with those from simulations with limited sample sizes. To create realistic correlations among multiple confounders, we also based simulations on a real dataset. Copyright © 2015 John Wiley & Sons, Ltd.

External adjustment sensitivity analysis for unmeasured confounding: an application to coronary stent outcomes, Pennsylvania 2004-2008.

PubMed

Huesch, Marco D

2013-06-01

Assessing the real-world comparative effectiveness of common interventions is challenged by unmeasured confounding. To determine whether the mortality benefit shown for drug-eluting stents (DES) over bare metal stents (BMS) in observational studies persists after controls for/tests for confounding. Retrospective observational study involving 38,019 patients, 65 years or older admitted for an index percutaneous coronary intervention receiving DES or BMS in Pennsylvania in 2004-2005 followed up for death through 3 years. Analysis was at the patient level. Mortality was analyzed with Cox proportional hazards models allowing for stratification by disease severity or DES use propensity, accounting for clustering of patients. Instrumental variables analysis used lagged physician stent usage to proxy for the focal stent type decision. A method originating in work by Cornfield and others in 1954 and popularized by Greenland in 1996 was used to assess robustness to confounding. DES was associated with a significantly lower adjusted risk of death at 3 years in Cox and in instrumented analyses. An implausibly strong hypothetical unobserved confounder would be required to fully explain these results. Confounding by indication can bias observational studies. No strong evidence of such selection biases was found in the reduced risk of death among elderly patients receiving DES instead of BMS in a Pennsylvanian state-wide population. © Health Research and Educational Trust.

Neuropsychological functioning in older people with type 2 diabetes: the effect of controlling for confounding factors.

PubMed

Asimakopoulou, K G; Hampson, S E; Morrish, N J

2002-04-01

Neuropsychological functioning was examined in a group of 33 older (mean age 62.40 +/- 9.62 years) people with Type 2 diabetes (Group 1) and 33 non-diabetic participants matched with Group 1 on age, sex, premorbid intelligence and presence of hypertension and cardio/cerebrovascular conditions (Group 2). Data statistically corrected for confounding factors obtained from the diabetic group were compared with the matched control group. The results suggested small cognitive deficits in diabetic people's verbal memory and mental flexibility (Logical Memory A and SS7). No differences were seen between the two samples in simple and complex visuomotor attention, sustained complex visual attention, attention efficiency, mental double tracking, implicit memory, and self-reported memory problems. These findings indicate minimal cognitive impairment in relatively uncomplicated Type 2 diabetes and demonstrate the importance of control and matching for confounding factors.

Using ecological propensity score to adjust for missing confounders in small area studies.

PubMed

Wang, Yingbo; Pirani, Monica; Hansell, Anna L; Richardson, Sylvia; Blangiardo, Marta

2017-11-09

Small area ecological studies are commonly used in epidemiology to assess the impact of area level risk factors on health outcomes when data are only available in an aggregated form. However, the resulting estimates are often biased due to unmeasured confounders, which typically are not available from the standard administrative registries used for these studies. Extra information on confounders can be provided through external data sets such as surveys or cohorts, where the data are available at the individual level rather than at the area level; however, such data typically lack the geographical coverage of administrative registries. We develop a framework of analysis which combines ecological and individual level data from different sources to provide an adjusted estimate of area level risk factors which is less biased. Our method (i) summarizes all available individual level confounders into an area level scalar variable, which we call ecological propensity score (EPS), (ii) implements a hierarchical structured approach to impute the values of EPS whenever they are missing, and (iii) includes the estimated and imputed EPS into the ecological regression linking the risk factors to the health outcome. Through a simulation study, we show that integrating individual level data into small area analyses via EPS is a promising method to reduce the bias intrinsic in ecological studies due to unmeasured confounders; we also apply the method to a real case study to evaluate the effect of air pollution on coronary heart disease hospital admissions in Greater London. © The Author 2017. Published by Oxford University Press.

A causal examination of the effects of confounding factors on multimetric indices

USGS Publications Warehouse

Schoolmaster, Donald R.; Grace, James B.; Schweiger, E. William; Mitchell, Brian R.; Guntenspergen, Glenn R.

2013-01-01

The development of multimetric indices (MMIs) as a means of providing integrative measures of ecosystem condition is becoming widespread. An increasingly recognized problem for the interpretability of MMIs is controlling for the potentially confounding influences of environmental covariates. Most common approaches to handling covariates are based on simple notions of statistical control, leaving the causal implications of covariates and their adjustment unstated. In this paper, we use graphical models to examine some of the potential impacts of environmental covariates on the observed signals between human disturbance and potential response metrics. Using simulations based on various causal networks, we show how environmental covariates can both obscure and exaggerate the effects of human disturbance on individual metrics. We then examine from a causal interpretation standpoint the common practice of adjusting ecological metrics for environmental influences using only the set of sites deemed to be in reference condition. We present and examine the performance of an alternative approach to metric adjustment that uses the whole set of sites and models both environmental and human disturbance effects simultaneously. The findings from our analyses indicate that failing to model and adjust metrics can result in a systematic bias towards those metrics in which environmental covariates function to artificially strengthen the metric–disturbance relationship resulting in MMIs that do not accurately measure impacts of human disturbance. We also find that a “whole-set modeling approach” requires fewer assumptions and is more efficient with the given information than the more commonly applied “reference-set” approach.

An assessment of the possible extent of confounding in epidemiological studies of lung cancer risk among roofers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mundt, D.J.; van Wijngaarden, E.; Mundt, K.A.

2007-07-01

We evaluated the likelihood and extent to which the observed increased risk of lung cancer may be due to confounding (a mixing of effects of multiple exposures) by co-exposure to other potential carcinogens present in roofing or to lifestyle variables. We conducted a review of the epidemiological and industrial hygiene literature of asphalt-exposed workers. Peer-reviewed epidemiological studies of asphalt fumes, related occupational exposures, and confounding factors were identified from MEDLINE (1966 early 2004). Industrial hygiene studies of asphalt workers were identified through MEDLINE, publicly available government documents, and asphalt industry documents. Using well established statistical methods, we quantified the extentmore » to which lung cancer relative risk estimates among roofers reflect confounding from other exposures, using different prevalence and risk scenarios. The relative risk of lung cancer varied from 1.2 to 5.0 in 13 epidemiological studies of roofers; most studies reported a relative risk between 1.2 and 1.4. Smoking, asbestos and coal tar were the most likely confounders, but the prevalence of these factors varied over time. The results of the study indicate that much of the observed risk reported in epidemiological studies of cancer among roofers is well within the range of what may have resulted from confounding by reasonable and expected levels of smoking, asbestos or coal tar. This may be particularly true for those studies that did not adjust for these confounders and where the exposure was defined as employment in the roofing industry. In addition to poorly defined asphalt exposure, uncontrolled confounding cannot reliably be ruled out in studies of lung cancer among asphalt-exposed roofers. Therefore, it is not possible to conclude whether roofers are at increased risk of lung cancer due to asphalt exposure.« less

Corticospinal activation confounds cerebellar effects of posterior fossa stimuli.

PubMed

Fisher, Karen M; Lai, H Ming; Baker, Mark R; Baker, Stuart N

2009-12-01

To investigate the efficacy of magnetic stimulation over the posterior fossa (PF) as a non-invasive assessment of cerebellar function in man. We replicated a previously reported conditioning-test paradigm in 11 healthy subjects. Transcranial magnetic stimulation (TMS) at varying intensities was applied to the PF and motor cortex with a 3, 5 or 7 ms interstimulus interval (ISI), chosen randomly for each trial. Surface electromyogram (EMG) activity was recorded from two intrinsic hand muscles and two forearm muscles. Responses were averaged and rectified, and MEP amplitudes were compared to assess whether suppression of the motor output occurred as a result of the PF conditioning pulse. Cortical MEPs were suppressed following conditioning-test ISIs of 5 or 7 ms. No suppression occurred with an ISI of 3 ms. PF stimuli alone also produced EMG responses, suggesting direct activation of the corticospinal tract (CST). CST collaterals are known to contact cortical inhibitory interneurones; antidromic CST activation could therefore contribute to the observed suppression of cortical MEPs. PF stimulation probably activates multiple pathways; even at low intensities it should not be regarded as a selective assessment of cerebellar function unless stringent controls can confirm the absence of confounding activity in other pathways.

Parenting Practices at 24 to 47 Months and IQ at Age 8: Effect-Measure Modification by Infant Temperament

PubMed Central

Chong, Shiau Yun; Chittleborough, Catherine R.; Gregory, Tess; Mittinty, Murthy N.; Lynch, John W.; Smithers, Lisa G.

2016-01-01

Cognitive development might be influenced by parenting practices and child temperament. We examined whether the associations between parental warmth, control and intelligence quotient (IQ) may be heightened among children in difficult temperament. Participants were from the Avon Longitudinal Study of Parents and Children (n = 7,044). Temperament at 6 months was measured using the Revised Infant Temperament Questionnaire and classified into ‘easy’ and ‘difficult’. Parental warmth and control was measured at 24 to 47 months and both were classified into 2 groups using latent class analyses. IQ was measured at 8 years using the Wechsler Intelligence Scale for Children and dichotomized (<85 and ≥85) for analyzing effect-measure modification by temperament. Linear regression adjusted for multiple confounders and temperament showed lower parental warmth was weakly associated with lower IQ score [β = -0.52 (95% CI 1.26, 0.21)], and higher parental control was associated with lower IQ score [β = -2.21 (-2.95, -1.48)]. Stratification by temperament showed no increased risk of having low IQ in temperamentally difficult children [risk ratio (RR) = 0.97 95% CI 0.65, 1.45)] but an increased risk among temperamentally easy children (RR = 1.12 95% CI 0.95, 1.32) when parental warmth was low. There was also no increased risk of having low IQ in temperamentally difficult children (RR = 1.02 95% CI 0.69, 1.53) but there was an increased risk among temperamentally easy children (RR = 1.30 95% CI 1.11, 1.53) when parental control was high. For both parental warmth and control, there was some evidence of negative effect-measure modification by temperament on the risk-difference scale and the risk-ratio scale. It may be more appropriate to provide parenting interventions as a universal program rather than targeting children with difficult temperament. PMID:27027637

Using instrumental variables to disentangle treatment and placebo effects in blinded and unblinded randomized clinical trials influenced by unmeasured confounders

NASA Astrophysics Data System (ADS)

Chaibub Neto, Elias

2016-11-01

Clinical trials traditionally employ blinding as a design mechanism to reduce the influence of placebo effects. In practice, however, it can be difficult or impossible to blind study participants and unblinded trials are common in medical research. Here we show how instrumental variables can be used to quantify and disentangle treatment and placebo effects in randomized clinical trials comparing control and active treatments in the presence of confounders. The key idea is to use randomization to separately manipulate treatment assignment and psychological encouragement conversations/interactions that increase the participants’ desire for improved symptoms. The proposed approach is able to improve the estimation of treatment effects in blinded studies and, most importantly, opens the doors to account for placebo effects in unblinded trials.

Beyond total treatment effects in randomised controlled trials: Baseline measurement of intermediate outcomes needed to reduce confounding in mediation investigations.

PubMed

Landau, Sabine; Emsley, Richard; Dunn, Graham

2018-06-01

Random allocation avoids confounding bias when estimating the average treatment effect. For continuous outcomes measured at post-treatment as well as prior to randomisation (baseline), analyses based on (A) post-treatment outcome alone, (B) change scores over the treatment phase or (C) conditioning on baseline values (analysis of covariance) provide unbiased estimators of the average treatment effect. The decision to include baseline values of the clinical outcome in the analysis is based on precision arguments, with analysis of covariance known to be most precise. Investigators increasingly carry out explanatory analyses to decompose total treatment effects into components that are mediated by an intermediate continuous outcome and a non-mediated part. Traditional mediation analysis might be performed based on (A) post-treatment values of the intermediate and clinical outcomes alone, (B) respective change scores or (C) conditioning on baseline measures of both intermediate and clinical outcomes. Using causal diagrams and Monte Carlo simulation, we investigated the performance of the three competing mediation approaches. We considered a data generating model that included three possible confounding processes involving baseline variables: The first two processes modelled baseline measures of the clinical variable or the intermediate variable as common causes of post-treatment measures of these two variables. The third process allowed the two baseline variables themselves to be correlated due to past common causes. We compared the analysis models implied by the competing mediation approaches with this data generating model to hypothesise likely biases in estimators, and tested these in a simulation study. We applied the methods to a randomised trial of pragmatic rehabilitation in patients with chronic fatigue syndrome, which examined the role of limiting activities as a mediator. Estimates of causal mediation effects derived by approach (A) will be biased if one of

Depression and Physical Inactivity as Confounding the Effect of Obesity on Atrial Fibrillation.

PubMed

Garimella, Roja S; Sears, Samuel F; Gehi, Anil K

2016-06-01

Obesity is associated with an increased likelihood for the development of atrial fibrillation (AF) and with worsened AF symptom severity. However, other factors that are correlated with obesity may confound or mediate the relation of obesity with AF symptom severity. The purpose of this study was to determine if depression and physical inactivity may confound the association of obesity and AF symptom severity. Health status and demographic data were captured by questionnaire for 332 outpatients with documented AF. Weight/height was measured and body mass index (kg/m(2)) calculated. Recent depression symptom severity was assessed using the Patient Health Questionnaire-9 questionnaire. Physical activity during the last month was assessed by questionnaire. AF symptom severity was assessed using the University of Toronto AF Severity scale. Multivariate linear regression was used to evaluate which factors were associated with AF symptom severity. Obesity in patients with AF is associated with increased depression severity. In bivariate analysis, increasing body mass index (p = 0.001), lower levels of physical activity (p <0.001), and more severe depression (p <0.001) were associated with worsened AF symptom severity. In multivariate analysis, only physical activity and depression persisted as significant predictors of AF symptom severity. In conclusion, although obesity likely contributes to the substrate predisposing to the development of AF, other factors may contribute to or mediate the worsened AF symptoms associated with obesity. Depression symptoms and physical inactivity, factors closely correlated with obesity, may exacerbate symptoms in patients with AF. Copyright © 2016 Elsevier Inc. All rights reserved.

The relationship between urinary tract infection during pregnancy and preeclampsia: causal, confounded or spurious?

PubMed

Karmon, Anatte; Sheiner, Eyal

2008-06-01

Preeclampsia is a major cause of maternal morbidity, although its precise etiology remains elusive. A number of studies suggest that urinary tract infection (UTI) during the course of gestation is associated with elevated risk for preeclampsia, while others have failed to prove such an association. In our medical center, pregnant women who were exposed to at least one UTI episode during pregnancy were 1.3 times more likely to have mild preeclampsia and 1.8 times more likely to have severe preeclampsia as compared to unexposed women. Our results are based on univariate analyses and are not adjusted for potential confounders. This editorial aims to discuss the relationship between urinary tract infection and preeclampsia, as well as examine the current problems regarding the interpretation of this association. Although the relationship between UTI and preeclampsia has been demonstrated in studies with various designs, carried-out in a variety of settings, the nature of this association is unclear. By taking into account timeline, dose-response effects, treatment influences, and potential confounders, as well as by neutralizing potential biases, future studies may be able to clarify the relationship between UTI and preeclampsia by determining if it is causal, confounded, or spurious.

Effect of water quality and confounding factors on digestive enzyme activities in Gammarus fossarum.

PubMed

Charron, L; Geffard, O; Chaumot, A; Coulaud, R; Queau, H; Geffard, A; Dedourge-Geffard, O

2013-12-01

The feeding activity and subsequent assimilation of the products resulting from food digestion allow organisms to obtain energy for growth, maintenance and reproduction. Among these biological parameters, we studied digestive enzymes (amylase, cellulase and trypsin) in Gammarus fossarum to assess the impact of contaminants on their access to energy resources. However, to enable objective assessment of a toxic effect of decreased water quality on an organisms' digestive capacity, it is necessary to establish reference values based on its natural variability as a function of changing biotic and abiotic factors. To limit the confounding influence of biotic factors, a caging approach with calibrated male organisms from the same population was used. This study applied an in situ deployment at 23 sites of the Rhone basin rivers, complemented by a laboratory experiment assessing the influence of two abiotic factors (temperature and conductivity). The results showed a small effect of conductivity on cellulase activity and a significant effect of temperature on digestive enzyme activity but only at the lowest temperature (7 °C). The experimental conditions allowed us to define an environmental reference value for digestive enzyme activities to select sites where the quality of the water impacted the digestive capacity of the organisms. In addition to the feeding rate, this study showed the relevance of digestive enzymes as biomarkers to be used as an early warning tool to reflect organisms' health and the chemical quality of aquatic ecosystems.

Asthma and atopy in children born by caesarean section: effect modification by family history of allergies - a population based cross-sectional study.

PubMed

Kolokotroni, Ourania; Middleton, Nicos; Gavatha, Marina; Lamnisos, Demetris; Priftis, Kostas N; Yiallouros, Panayiotis K

2012-11-16

Studies on the association of birth by caesarean section (C/S) and allergies have produced conflicting findings. Furthermore, evidence on whether this association may differ in those at risk of atopy is limited. This study aims to investigate the association of mode of delivery with asthma and atopic sensitization and the extent to which any effect is modified by family history of allergies. Asthma outcomes were assessed cross-sectionally in 2216 children at age 8 on the basis of parents' responses to the ISAAC questionnaire whilst skin prick tests to eleven aeroallergens were also performed in a subgroup of 746 children. Adjusted odds ratios of asthma and atopy by mode of delivery were estimated in multivariable logistic models while evidence of effect modification was examined by introducing interaction terms in the models. After adjusting for potential confounders, children born by C/S appeared significantly more likely than those born vaginally to report ever wheezing (OR 1.36, 95% CI 1.07-1.71), asthma diagnosis (OR 1.41, 95% CI 1.09-1.83) and be atopic (OR 1.67, 95% CI 1.08-2.60). There was modest evidence that family history of allergies may modify the effect of C/S delivery on atopy (p for effect modification=0.06) but this was not the case for the asthma outcomes. Specifically, while more than a two-fold increase in the odds of being a topic was observed in children with a family history of allergies if born by C/S (OR 2.62, 95% CI 1.38-5.00), no association was observed in children without a family history of allergies (OR 1.16, 95% CI 0.64-2.11). Birth by C/S is associated with asthma and atopic sensitization in childhood. The association of C/S and atopy appears more pronounced in children with family history of allergies.

Combined effect of short-term dehydration and sublethal acute oral dicrotophos exposure confounds the diagnosis of anticholinesterase exposure in common quail (Coturnix coturnix) using plasma cholinesterase activity.

PubMed

Heffernan, James; Mineau, Pierre; Falk, Ramona; Wickstrom, Mark

2012-07-01

Common Quail (Coturnix coturnix) were subjected to controlled and replicated experiments in the summer of 2008 to investigate the effects of short-term dehydration on cholinesterase activity in brain and plasma and the interaction between dehydration and exposure to the organophosphorus pesticide dicrotophos in these same tissues. Our objective was to determine if dehydration could confound the diagnosis of anticholinesterase exposure using inhibition of cholinesterase activity in quail tissues. The effect of dehydration was quantified using measures of plasma osmolality and hematocrit. Dicrotophos exposure caused significant inhibition of cholinesterase activity in brain, while the effects of dehydration and interaction were not significant. Dehydration caused significant duration-dependent increases in plasma osmolality and hematocrit. Dehydration also caused a significant increase in plasma cholinesterase activity. Variation in the change in plasma cholinesterase activity in response to dehydration was significantly and positively correlated with dehydration-induced variation in both the change in plasma osmolality and the change in hematocrit. These correlations suggest that plasma cholinesterase activity in quail is not limited to plasma but occupies some larger pool of the extracellular fluid volume, and we suggest lymph is part of that pool. The effects of dehydration on plasma cholinesterase activity masked the inhibitory effects of dicrotophos. Here, the combination of dehydration and dicrotophos exposure produced plasma cholinesterase activity that was not significantly different from reference and pre-exposure values, confounding the diagnosis of anticholinesterase exposure in dehydrated, dicrotophos-exposed quail. A method to adjust plasma cholinesterase activities for the confounding effects of dehydration and enable the diagnosis of anticholinesterase exposure in dehydrated, dicrotophos-exposed quail was developed. Clinicians and practitioners

Confounding by dietary patterns of the inverse association between alcohol consumption and type 2 diabetes risk.

PubMed

Imamura, Fumiaki; Lichtenstein, Alice H; Dallal, Gerard E; Meigs, James B; Jacques, Paul F

2009-07-01

The ability to interpret epidemiologic observations is limited because of potential residual confounding by correlated dietary components. Dietary pattern analyses by factor analysis or partial least squares may overcome the limitation. To examine confounding by dietary pattern as well as standard risk factors and selected nutrients, the authors modeled the longitudinal association between alcohol consumption and 7-year risk of type 2 diabetes mellitus in 2,879 healthy adults enrolled in the Framingham Offspring Study (1991-2001) by Cox proportional hazard models. After adjustment for standard risk factors, consumers of > or =9.0 drinks/week had a significantly lower risk of type 2 diabetes mellitus compared with abstainers (hazard ratio = 0.47, 95% confidence interval (CI): 0.27, 0.81). Adjustment for selected nutrients had little effect on the hazard ratio, whereas adjustment for dietary pattern variables by factor analysis significantly shifted the hazard ratio away from null (hazard ratio = 0.33, 95% CI: 0.17, 0.64) by 40.0% (95% CI: 16.8, 57.0; P = 0.002). Dietary pattern variables by partial least squares showed similar results. Therefore, the observed inverse association, consistent with past studies, was confounded by dietary patterns, and this confounding was not captured by individual nutrient adjustment. The data suggest that alcohol intake, not dietary patterns associated with alcohol intake, is responsible for the observed inverse association with type 2 diabetes mellitus risk.

On causal interpretation of race in regressions adjusting for confounding and mediating variables

PubMed Central

VanderWeele, Tyler J.; Robinson, Whitney R.

2014-01-01

We consider several possible interpretations of the “effect of race” when regressions are run with race as an exposure variable, controlling also for various confounding and mediating variables. When adjustment is made for socioeconomic status early in a person’s life, we discuss under what contexts the regression coefficients for race can be interpreted as corresponding to the extent to which a racial inequality would remain if various socioeconomic distributions early in life across racial groups could be equalized. When adjustment is also made for adult socioeconomic status, we note how the overall racial inequality can be decomposed into the portion that would be eliminated by equalizing adult socioeconomic status across racial groups and the portion of the inequality that would remain even if adult socioeconomic status across racial groups were equalized. We also discuss a stronger interpretation of the “effect of race” (stronger in terms of assumptions) involving the joint effects of race-associated physical phenotype (e.g. skin color), parental physical phenotype, genetic background and cultural context when such variables are thought to be hypothetically manipulable and if adequate control for confounding were possible. We discuss some of the challenges with such an interpretation. Further discussion is given as to how the use of selected populations in examining racial disparities can additionally complicate the interpretation of the effects. PMID:24887159

Measurement error, time lag, unmeasured confounding: Considerations for longitudinal estimation of the effect of a mediator in randomised clinical trials.

PubMed

Goldsmith, K A; Chalder, T; White, P D; Sharpe, M; Pickles, A

2018-06-01

Clinical trials are expensive and time-consuming and so should also be used to study how treatments work, allowing for the evaluation of theoretical treatment models and refinement and improvement of treatments. These treatment processes can be studied using mediation analysis. Randomised treatment makes some of the assumptions of mediation models plausible, but the mediator-outcome relationship could remain subject to bias. In addition, mediation is assumed to be a temporally ordered longitudinal process, but estimation in most mediation studies to date has been cross-sectional and unable to explore this assumption. This study used longitudinal structural equation modelling of mediator and outcome measurements from the PACE trial of rehabilitative treatments for chronic fatigue syndrome (ISRCTN 54285094) to address these issues. In particular, autoregressive and simplex models were used to study measurement error in the mediator, different time lags in the mediator-outcome relationship, unmeasured confounding of the mediator and outcome, and the assumption of a constant mediator-outcome relationship over time. Results showed that allowing for measurement error and unmeasured confounding were important. Contemporaneous rather than lagged mediator-outcome effects were more consistent with the data, possibly due to the wide spacing of measurements. Assuming a constant mediator-outcome relationship over time increased precision.

Measurement error, time lag, unmeasured confounding: Considerations for longitudinal estimation of the effect of a mediator in randomised clinical trials

PubMed Central

Goldsmith, KA; Chalder, T; White, PD; Sharpe, M; Pickles, A

2016-01-01

Clinical trials are expensive and time-consuming and so should also be used to study how treatments work, allowing for the evaluation of theoretical treatment models and refinement and improvement of treatments. These treatment processes can be studied using mediation analysis. Randomised treatment makes some of the assumptions of mediation models plausible, but the mediator–outcome relationship could remain subject to bias. In addition, mediation is assumed to be a temporally ordered longitudinal process, but estimation in most mediation studies to date has been cross-sectional and unable to explore this assumption. This study used longitudinal structural equation modelling of mediator and outcome measurements from the PACE trial of rehabilitative treatments for chronic fatigue syndrome (ISRCTN 54285094) to address these issues. In particular, autoregressive and simplex models were used to study measurement error in the mediator, different time lags in the mediator–outcome relationship, unmeasured confounding of the mediator and outcome, and the assumption of a constant mediator–outcome relationship over time. Results showed that allowing for measurement error and unmeasured confounding were important. Contemporaneous rather than lagged mediator–outcome effects were more consistent with the data, possibly due to the wide spacing of measurements. Assuming a constant mediator–outcome relationship over time increased precision. PMID:27647810

A powerful and efficient set test for genetic markers that handles confounders

PubMed Central

Listgarten, Jennifer; Lippert, Christoph; Kang, Eun Yong; Xiang, Jing; Kadie, Carl M.; Heckerman, David

2013-01-01

Motivation: Approaches for testing sets of variants, such as a set of rare or common variants within a gene or pathway, for association with complex traits are important. In particular, set tests allow for aggregation of weak signal within a set, can capture interplay among variants and reduce the burden of multiple hypothesis testing. Until now, these approaches did not address confounding by family relatedness and population structure, a problem that is becoming more important as larger datasets are used to increase power. Results: We introduce a new approach for set tests that handles confounders. Our model is based on the linear mixed model and uses two random effects—one to capture the set association signal and one to capture confounders. We also introduce a computational speedup for two random-effects models that makes this approach feasible even for extremely large cohorts. Using this model with both the likelihood ratio test and score test, we find that the former yields more power while controlling type I error. Application of our approach to richly structured Genetic Analysis Workshop 14 data demonstrates that our method successfully corrects for population structure and family relatedness, whereas application of our method to a 15 000 individual Crohn’s disease case–control cohort demonstrates that it additionally recovers genes not recoverable by univariate analysis. Availability: A Python-based library implementing our approach is available at http://mscompbio.codeplex.com. Contact: jennl@microsoft.com or lippert@microsoft.com or heckerma@microsoft.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23599503

Effects of ionospheric modification on system performance

NASA Astrophysics Data System (ADS)

Ganguly, Suman

1989-12-01

Controlled ionospheric modification can be used for disrupting as well as facilitating communication and radar systems. After briefly describing the results achieved with the present day ionospheric modification facilities, a scenario is presented for the generation of strong and significant ionospheric modification. A few schemes are presented for the development of modern high power facilities using the state of the art technology and then the impact of such facilities on the system performance is described.

Investigation of the Effect of Oil Modification on Critical Characteristics of Asphalt Binders

NASA Astrophysics Data System (ADS)

Golalipour, Amir

Thermally induced cracking of asphalt pavement continues to be a serious issue in cold climate regions as well as in areas which experience extreme daily temperature differentials. Low temperature cracking of asphalt pavements is attributed to thermal stresses and strains developed during cooling cycles. Improving asphalt binder low temperature fracture and stiffness properties continues to be a subject of particular concern. Therefore, significant amount of research has been focused on improving asphalt binder properties through modification. In recent years, wide ranges of oil based modifications have been introduced to improve asphalt binder performance, especially at the low service temperatures. Although, significant use of these oils is seen in practice, knowledge of the fundamental mechanisms of oil modification and their properties for achieving optimum characteristics is limited. Hence, this study focuses on better understanding of the effect of oil modifiers which would help better material selection and achieve optimum performance in terms of increasing the life span of pavements. In this study, the effect of oil modification on the rheological properties of the asphalt binder is investigated. To examine the effect of oil modification on binder characteristics, low temperature properties as well as high temperature performance of oil modified binders were evaluated. It is found that oils vary in their effects on asphalt binder performance. However, for all oils used in the study, adding an oil to binder can improve binder low temperature performance, and this result mainly attributed to the softening effect. In addition to that, a simple linear model is proposed to predict the performance grade of oil modified binder based on the properties of its constituents at high and low temperatures. Another part of this study focuses on the oil modification effect on asphalt binder thermal strain and stresses. A viscoelastic analytical procedure is combined with

The confounded effects of age and exposure history in response to influenza vaccination

PubMed Central

Höpping, Ana Mosterín; McElhaney, Janet; Fonville, Judith M.; Powers, Douglas C.; Beyer, Walter E.P.; Smith, Derek J.

2016-01-01

Numerous studies have explored whether the antibody response to influenza vaccination in elderly adults is as strong as it is in young adults. Results vary, but tend to indicate lower post-vaccination titers (antibody levels) in the elderly, supporting the concept of immunosenescence – the weakening of the immunological response related to age. Because the elderly in such studies typically have been vaccinated against influenza before enrollment, a confounding of effects occurs between age, and previous exposures, as a potential extrinsic reason for immunosenescence. We conducted a four-year study of serial annual immunizations with inactivated trivalent influenza vaccines in 136 young adults (16 to 39 years) and 122 elderly adults (62 to 92 years). Compared to data sets of previously published studies, which were designed to investigate the effect of age, this detailed longitudinal study with multiple vaccinations allowed us to also study the effect of prior vaccination history on the response to a vaccine. In response to the first vaccination, young adults produced higher post-vaccination titers, accounting for pre-vaccination titers, than elderly adults. However, upon subsequent vaccinations the difference in response to vaccination between the young and elderly age groups declined rapidly. Although age is an important factor when modeling the outcome of the first vaccination, this term lost its relevance with successive vaccinations. In fact, when we examined the data with the assumption that the elderly group had received (on average) as few as two vaccinations prior to our study, the difference due to age disappeared. Our analyses therefore show that the initial difference between the two age groups in their response to vaccination may not be uniquely explained by immunosenescence due to ageing of the immune system, but could equally be the result of the different pre-study vaccination and infection histories in the elderly. PMID:26667611

Effects of tooth profile modification on dynamic responses of a high speed gear-rotor-bearing system

NASA Astrophysics Data System (ADS)

Hu, Zehua; Tang, Jinyuan; Zhong, Jue; Chen, Siyu; Yan, Haiyan

2016-08-01

A finite element node dynamic model of a high speed gear-rotor-bearing system considering the time-varying mesh stiffness, backlash, gyroscopic effect and transmission error excitation is developed. Different tooth profile modifications are introduced into the gear pair and corresponding time-varying mesh stiffness curves are obtained. Effects of the tooth profile modification on mesh stiffness are analyzed, and the natural frequencies and mode shapes of the gear-rotor-bearing transmission system are given. The dynamic responses with respect to a wide input speed region including dynamic factor, vibration amplitude near the bearing and dynamic transmission error are obtained by introducing the time-varying mesh stiffness in different tooth profile modification cases into the gear-rotor-bearing dynamic system. Effects of the tooth profile modification on the dynamic responses are studied in detail. The numerical simulation results show that both the short profile modification and the long profile modification can affect the mutation of the mesh stiffness when the number of engaging tooth pairs changes. A short profile modification with an appropriate modification amount can improve the dynamic property of the system in certain work condition.

Effects of wing modification on an aircraft's aerodynamic parameters as determined from flight data

NASA Technical Reports Server (NTRS)

Hess, R. A.

1986-01-01

A study of the effects of four wing-leading-edge modifications on a general aviation aircraft's stability and control parameters is presented. Flight data from the basic aircraft configuration and configurations with wing modifications are analyzed to determine each wing geometry's stability and control parameters. The parameter estimates and aerodynamic model forms are obtained using the stepwise regression and maximum likelihood techniques. The resulting parameter estimates and aerodynamic models are verified using vortex-lattice theory and by analysis of each model's ability to predict aircraft behavior. Comparisons of the stability and control derivative estimates from the basic wing and the four leading-edge modifications are accomplished so that the effects of each modification on aircraft stability and control derivatives can be determined.

Effect of edge modification on the zigzag BC2N nanoribbons

NASA Astrophysics Data System (ADS)

Xiao, Xiang; Li, Hong; Tie, Jun; Lu, Jing

2016-08-01

We use first principles calculations to investigate the effects of edge modification with nonmetal species on zigzag-edged BC2N nanoribbons (ZBC2NNRs). These ZBC2NNRs show either semiconducting or metallic behaviors depending on the edge modifications and ribbon widths. We find that the O-modification induces a ferromagnetic ground state with a metallic behavior for all the ribbon widths investigated. And when the ribbon width is more than 3.32 nm (NZ ⩾ 16), an antiferromagnetic ground state with a half-metallic behavior is realized in the H-passivated ZBC2NNRs. These versatile electronic properties render the ZBC2NNRs a promising candidate material in nanoelectronics and nanospintronics.

A sequential Cox approach for estimating the causal effect of treatment in the presence of time-dependent confounding applied to data from the Swiss HIV Cohort Study.

PubMed

Gran, Jon Michael; Røysland, Kjetil; Wolbers, Marcel; Didelez, Vanessa; Sterne, Jonathan A C; Ledergerber, Bruno; Furrer, Hansjakob; von Wyl, Viktor; Aalen, Odd O

2010-11-20

When estimating the effect of treatment on HIV using data from observational studies, standard methods may produce biased estimates due to the presence of time-dependent confounders. Such confounding can be present when a covariate, affected by past exposure, is both a predictor of the future exposure and the outcome. One example is the CD4 cell count, being a marker for disease progression for HIV patients, but also a marker for treatment initiation and influenced by treatment. Fitting a marginal structural model (MSM) using inverse probability weights is one way to give appropriate adjustment for this type of confounding. In this paper we study a simple and intuitive approach to estimate similar treatment effects, using observational data to mimic several randomized controlled trials. Each 'trial' is constructed based on individuals starting treatment in a certain time interval. An overall effect estimate for all such trials is found using composite likelihood inference. The method offers an alternative to the use of inverse probability of treatment weights, which is unstable in certain situations. The estimated parameter is not identical to the one of an MSM, it is conditioned on covariate values at the start of each mimicked trial. This allows the study of questions that are not that easily addressed fitting an MSM. The analysis can be performed as a stratified weighted Cox analysis on the joint data set of all the constructed trials, where each trial is one stratum. The model is applied to data from the Swiss HIV cohort study. Copyright © 2010 John Wiley & Sons, Ltd.

Ecological Effects of Weather Modification: A Problem Analysis.

ERIC Educational Resources Information Center

Cooper, Charles F.; Jolly, William C.

This publication reviews the potential hazards to the environment of weather modification techniques as they eventually become capable of producing large scale weather pattern modifications. Such weather modifications could result in ecological changes which would generally require several years to be fully evident, including the alteration of…

A stratification approach using logit-based models for confounder adjustment in the study of continuous outcomes.

PubMed

Tan, Chuen Seng; Støer, Nathalie C; Chen, Ying; Andersson, Marielle; Ning, Yilin; Wee, Hwee-Lin; Khoo, Eric Yin Hao; Tai, E-Shyong; Kao, Shih Ling; Reilly, Marie

2017-01-01

The control of confounding is an area of extensive epidemiological research, especially in the field of causal inference for observational studies. Matched cohort and case-control study designs are commonly implemented to control for confounding effects without specifying the functional form of the relationship between the outcome and confounders. This paper extends the commonly used regression models in matched designs for binary and survival outcomes (i.e. conditional logistic and stratified Cox proportional hazards) to studies of continuous outcomes through a novel interpretation and application of logit-based regression models from the econometrics and marketing research literature. We compare the performance of the maximum likelihood estimators using simulated data and propose a heuristic argument for obtaining the residuals for model diagnostics. We illustrate our proposed approach with two real data applications. Our simulation studies demonstrate that our stratification approach is robust to model misspecification and that the distribution of the estimated residuals provides a useful diagnostic when the strata are of moderate size. In our applications to real data, we demonstrate that parity and menopausal status are associated with percent mammographic density, and that the mean level and variability of inpatient blood glucose readings vary between medical and surgical wards within a national tertiary hospital. Our work highlights how the same class of regression models, available in most statistical software, can be used to adjust for confounding in the study of binary, time-to-event and continuous outcomes.

Do time-invariant confounders explain away the association between job stress and workers' mental health? Evidence from Japanese occupational panel data.

PubMed

Oshio, Takashi; Tsutsumi, Akizumi; Inoue, Akiomi

2015-02-01

It is well known that job stress is negatively related to workers' mental health, but most recent studies have not controlled for unobserved time-invariant confounders. In the current study, we attempted to validate previous observations on the association between job stress and workers' mental health, by removing the effects of unobserved time-invariant confounders. We used data from three to four waves of an occupational Japanese cohort survey, focusing on 31,382 observations of 9741 individuals who participated in at least two consecutive waves. We estimated mean-centered fixed effects models to explain psychological distress in terms of the Kessler 6 (K6) scores (range: 0-24) by eight job stress indicators related to the job demands-control, effort-reward imbalance, and organizational injustice models. Mean-centered fixed effects models reduced the magnitude of the association between jobs stress and K6 scores to 44.8-54.2% of those observed from pooled ordinary least squares. However, the association remained highly significant even after controlling for unobserved time-invariant confounders for all job stress indicators. In addition, alternatively specified models showed the robustness of the results. In all, we concluded that the validity of major job stress models, which link job stress and workers' mental health, was robust, although unobserved time-invariant confounders led to an overestimation of the association. Copyright © 2014 Elsevier Ltd. All rights reserved.

Batch Effect Confounding Leads to Strong Bias in Performance Estimates Obtained by Cross-Validation

PubMed Central

Delorenzi, Mauro

2014-01-01

Background With the large amount of biological data that is currently publicly available, many investigators combine multiple data sets to increase the sample size and potentially also the power of their analyses. However, technical differences (“batch effects”) as well as differences in sample composition between the data sets may significantly affect the ability to draw generalizable conclusions from such studies. Focus The current study focuses on the construction of classifiers, and the use of cross-validation to estimate their performance. In particular, we investigate the impact of batch effects and differences in sample composition between batches on the accuracy of the classification performance estimate obtained via cross-validation. The focus on estimation bias is a main difference compared to previous studies, which have mostly focused on the predictive performance and how it relates to the presence of batch effects. Data We work on simulated data sets. To have realistic intensity distributions, we use real gene expression data as the basis for our simulation. Random samples from this expression matrix are selected and assigned to group 1 (e.g., ‘control’) or group 2 (e.g., ‘treated’). We introduce batch effects and select some features to be differentially expressed between the two groups. We consider several scenarios for our study, most importantly different levels of confounding between groups and batch effects. Methods We focus on well-known classifiers: logistic regression, Support Vector Machines (SVM), k-nearest neighbors (kNN) and Random Forests (RF). Feature selection is performed with the Wilcoxon test or the lasso. Parameter tuning and feature selection, as well as the estimation of the prediction performance of each classifier, is performed within a nested cross-validation scheme. The estimated classification performance is then compared to what is obtained when applying the classifier to independent data. PMID:24967636

Surface modification effects on defect-related photoluminescence in colloidal CdS quantum dots.

PubMed

Lee, TaeGi; Shimura, Kunio; Kim, DaeGwi

2018-05-03

We investigated the effects of surface modification on the defect-related photoluminescence (PL) band in colloidal CdS quantum dots (QDs). A size-selective photoetching process and a surface modification technique with a Cd(OH)2 layer enabled the preparation of size-controlled CdS QDs with high PL efficiency. The Stokes shift of the defect-related PL band before and after the surface modification was ∼1.0 eV and ∼0.63 eV, respectively. This difference in the Stokes shifts suggests that the origin of the defect-related PL band was changed by the surface modification. Analysis by X-ray photoelectron spectroscopy revealed that the surface of the CdS QDs before and after the surface modification was S rich and Cd rich, respectively. These results suggest that Cd-vacancy acceptors and S-vacancy donors affect PL processes in CdS QDs before and after the surface modification, respectively.

An independent component analysis confounding factor correction framework for identifying broad impact expression quantitative trait loci

PubMed Central

Ju, Jin Hyun; Crystal, Ronald G.

2017-01-01

Genome-wide expression Quantitative Trait Loci (eQTL) studies in humans have provided numerous insights into the genetics of both gene expression and complex diseases. While the majority of eQTL identified in genome-wide analyses impact a single gene, eQTL that impact many genes are particularly valuable for network modeling and disease analysis. To enable the identification of such broad impact eQTL, we introduce CONFETI: Confounding Factor Estimation Through Independent component analysis. CONFETI is designed to address two conflicting issues when searching for broad impact eQTL: the need to account for non-genetic confounding factors that can lower the power of the analysis or produce broad impact eQTL false positives, and the tendency of methods that account for confounding factors to model broad impact eQTL as non-genetic variation. The key advance of the CONFETI framework is the use of Independent Component Analysis (ICA) to identify variation likely caused by broad impact eQTL when constructing the sample covariance matrix used for the random effect in a mixed model. We show that CONFETI has better performance than other mixed model confounding factor methods when considering broad impact eQTL recovery from synthetic data. We also used the CONFETI framework and these same confounding factor methods to identify eQTL that replicate between matched twin pair datasets in the Multiple Tissue Human Expression Resource (MuTHER), the Depression Genes Networks study (DGN), the Netherlands Study of Depression and Anxiety (NESDA), and multiple tissue types in the Genotype-Tissue Expression (GTEx) consortium. These analyses identified both cis-eQTL and trans-eQTL impacting individual genes, and CONFETI had better or comparable performance to other mixed model confounding factor analysis methods when identifying such eQTL. In these analyses, we were able to identify and replicate a few broad impact eQTL although the overall number was small even when applying CONFETI. In

An independent component analysis confounding factor correction framework for identifying broad impact expression quantitative trait loci.

PubMed

Ju, Jin Hyun; Shenoy, Sushila A; Crystal, Ronald G; Mezey, Jason G

2017-05-01

Genome-wide expression Quantitative Trait Loci (eQTL) studies in humans have provided numerous insights into the genetics of both gene expression and complex diseases. While the majority of eQTL identified in genome-wide analyses impact a single gene, eQTL that impact many genes are particularly valuable for network modeling and disease analysis. To enable the identification of such broad impact eQTL, we introduce CONFETI: Confounding Factor Estimation Through Independent component analysis. CONFETI is designed to address two conflicting issues when searching for broad impact eQTL: the need to account for non-genetic confounding factors that can lower the power of the analysis or produce broad impact eQTL false positives, and the tendency of methods that account for confounding factors to model broad impact eQTL as non-genetic variation. The key advance of the CONFETI framework is the use of Independent Component Analysis (ICA) to identify variation likely caused by broad impact eQTL when constructing the sample covariance matrix used for the random effect in a mixed model. We show that CONFETI has better performance than other mixed model confounding factor methods when considering broad impact eQTL recovery from synthetic data. We also used the CONFETI framework and these same confounding factor methods to identify eQTL that replicate between matched twin pair datasets in the Multiple Tissue Human Expression Resource (MuTHER), the Depression Genes Networks study (DGN), the Netherlands Study of Depression and Anxiety (NESDA), and multiple tissue types in the Genotype-Tissue Expression (GTEx) consortium. These analyses identified both cis-eQTL and trans-eQTL impacting individual genes, and CONFETI had better or comparable performance to other mixed model confounding factor analysis methods when identifying such eQTL. In these analyses, we were able to identify and replicate a few broad impact eQTL although the overall number was small even when applying CONFETI. In

Residential proximity to electromagnetic field sources and birth weight: Minimizing residual confounding using multiple imputation and propensity score matching.

PubMed

de Vocht, Frank; Lee, Brian

2014-08-01

Studies have suggested that residential exposure to extremely low frequency (50 Hz) electromagnetic fields (ELF-EMF) from high voltage cables, overhead power lines, electricity substations or towers are associated with reduced birth weight and may be associated with adverse birth outcomes or even miscarriages. We previously conducted a study of 140,356 singleton live births between 2004 and 2008 in Northwest England, which suggested that close residential proximity (≤ 50 m) to ELF-EMF sources was associated with reduced average birth weight of 212 g (95%CI: -395 to -29 g) but not with statistically significant increased risks for other adverse perinatal outcomes. However, the cohort was limited by missing data for most potentially confounding variables including maternal smoking during pregnancy, which was only available for a small subgroup, while also residual confounding could not be excluded. This study, using the same cohort, was conducted to minimize the effects of these problems using multiple imputation to address missing data and propensity score matching to minimize residual confounding. Missing data were imputed using multiple imputation using chained equations to generate five datasets. For each dataset 115 exposed women (residing ≤ 50 m from a residential ELF-EMF source) were propensity score matched to 1150 unexposed women. After doubly robust confounder adjustment, close proximity to a residential ELF-EMF source remained associated with a reduction in birth weight of -116 g (95% confidence interval: -224:-7 g). No effect was found for proximity ≤ 100 m compared to women living further away. These results indicate that although the effect size was about half of the effect previously reported, close maternal residential proximity to sources of ELF-EMF remained associated with suboptimal fetal growth. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of tRNA modification on translational accuracy depend on intrinsic codon-anticodon strength.

PubMed

Manickam, Nandini; Joshi, Kartikeya; Bhatt, Monika J; Farabaugh, Philip J

2016-02-29

Cellular health and growth requires protein synthesis to be both efficient to ensure sufficient production, and accurate to avoid producing defective or unstable proteins. The background of misreading error frequency by individual tRNAs is as low as 2 × 10(-6) per codon but is codon-specific with some error frequencies above 10(-3) per codon. Here we test the effect on error frequency of blocking post-transcriptional modifications of the anticodon loops of four tRNAs in Escherichia coli. We find two types of responses to removing modification. Blocking modification of tRNA(UUC)(Glu) and tRNA(QUC)(Asp) increases errors, suggesting that the modifications act at least in part to maintain accuracy. Blocking even identical modifications of tRNA(UUU)(Lys) and tRNA(QUA)(Tyr) has the opposite effect of decreasing errors. One explanation could be that the modifications play opposite roles in modulating misreading by the two classes of tRNAs. Given available evidence that modifications help preorder the anticodon to allow it to recognize the codons, however, the simpler explanation is that unmodified 'weak' tRNAs decode too inefficiently to compete against cognate tRNAs that normally decode target codons, which would reduce the frequency of misreading. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Pot binding as a variable confounding plant phenotype: theoretical derivation and experimental observations.

PubMed

Sinclair, Thomas R; Manandhar, Anju; Shekoofa, Avat; Rosas-Anderson, Pablo; Bagherzadi, Laleh; Schoppach, Remy; Sadok, Walid; Rufty, Thomas W

2017-04-01

Theoretical derivation predicted growth retardation due to pot water limitations, i.e., pot binding. Experimental observations were consistent with these limitations. Combined, these results indicate a need for caution in high-throughput screening and phenotyping. Pot experiments are a mainstay in many plant studies, including the current emphasis on developing high-throughput, phenotyping systems. Pot studies can be vulnerable to decreased physiological activity of the plants particularly when pot volume is small, i.e., "pot binding". It is necessary to understand the conditions under which pot binding may exist to avoid the confounding influence of pot binding in interpreting experimental results. In this paper, a derivation is offered that gives well-defined conditions for the occurrence of pot binding based on restricted water availability. These results showed that not only are pot volume and plant size important variables, but the potting media is critical. Artificial potting mixtures used in many studies, including many high-throughput phenotyping systems, are particularly susceptible to the confounding influences of pot binding. Experimental studies for several crop species are presented that clearly show the existence of thresholds of plant leaf area at which various pot sizes and potting media result in the induction of pot binding even though there may be no immediate, visual plant symptoms. The derivation and experimental results showed that pot binding can readily occur in plant experiments if care is not given to have sufficiently large pots, suitable potting media, and maintenance of pot water status. Clear guidelines are provided for avoiding the confounding effects of water-limited pot binding in studying plant phenotype.

The Effects of Approach-Avoidance Modification on Social Anxiety Disorder: A Pilot Study

PubMed Central

Asnaani, Anu; Rinck, Mike; Becker, Eni; Hofmann, Stefan G.

2014-01-01

Cognitive bias modification has recently been discussed as a possible intervention for mental disorders. A specific form of this novel treatment approach is approach-avoidance modification. In order to examine the efficacy of approach-avoidance modification for positive stimuli associated with social anxiety, we recruited 43 individuals with social anxiety disorder and randomly assigned them to a training (implicit training to approach smiling faces) or a control (equal approach and avoidance of smiling faces) condition in three sessions over the course of a one-week period. Dependent measures included clinician ratings, self-report measures of social anxiety, and overt behavior during behavioral approach tasks. No group differences in any of the outcome measures were observed after training. In addition, while individuals in the training group showed increased approach tendency in one of the sessions, this effect was inconsistent across the three sessions and did not result in long-term changes in implicit approach tendencies between the groups over the course of the entire study. These results suggest that approach-avoidance modification might result in short-lasting effects on implicit approach tendencies towards feared positive stimuli, but this modification may not result in meaningful behavioral change or symptom reduction in individuals with social anxiety disorder. PMID:24659832

Analysis of Longitudinal Studies With Repeated Outcome Measures: Adjusting for Time-Dependent Confounding Using Conventional Methods.

PubMed

Keogh, Ruth H; Daniel, Rhian M; VanderWeele, Tyler J; Vansteelandt, Stijn

2018-05-01

Estimation of causal effects of time-varying exposures using longitudinal data is a common problem in epidemiology. When there are time-varying confounders, which may include past outcomes, affected by prior exposure, standard regression methods can lead to bias. Methods such as inverse probability weighted estimation of marginal structural models have been developed to address this problem. However, in this paper we show how standard regression methods can be used, even in the presence of time-dependent confounding, to estimate the total effect of an exposure on a subsequent outcome by controlling appropriately for prior exposures, outcomes, and time-varying covariates. We refer to the resulting estimation approach as sequential conditional mean models (SCMMs), which can be fitted using generalized estimating equations. We outline this approach and describe how including propensity score adjustment is advantageous. We compare the causal effects being estimated using SCMMs and marginal structural models, and we compare the two approaches using simulations. SCMMs enable more precise inferences, with greater robustness against model misspecification via propensity score adjustment, and easily accommodate continuous exposures and interactions. A new test for direct effects of past exposures on a subsequent outcome is described.

Distinguishing prostate cancer from benign confounders via a cascaded classifier on multi-parametric MRI

NASA Astrophysics Data System (ADS)

Litjens, G. J. S.; Elliott, R.; Shih, N.; Feldman, M.; Barentsz, J. O.; Hulsbergen-van de Kaa, C. A.; Kovacs, I.; Huisman, H. J.; Madabhushi, A.

2014-03-01

Learning how to separate benign confounders from prostate cancer is important because the imaging characteristics of these confounders are poorly understood. Furthermore, the typical representations of the MRI parameters might not be enough to allow discrimination. The diagnostic uncertainty this causes leads to a lower diagnostic accuracy. In this paper a new cascaded classifier is introduced to separate prostate cancer and benign confounders on MRI in conjunction with specific computer-extracted features to distinguish each of the benign classes (benign prostatic hyperplasia (BPH), inflammation, atrophy or prostatic intra-epithelial neoplasia (PIN). In this study we tried to (1) calculate different mathematical representations of the MRI parameters which more clearly express subtle differences between different classes, (2) learn which of the MRI image features will allow to distinguish specific benign confounders from prostate cancer, and (2) find the combination of computer-extracted MRI features to best discriminate cancer from the confounding classes using a cascaded classifier. One of the most important requirements for identifying MRI signatures for adenocarcinoma, BPH, atrophy, inflammation, and PIN is accurate mapping of the location and spatial extent of the confounder and cancer categories from ex vivo histopathology to MRI. Towards this end we employed an annotated prostatectomy data set of 31 patients, all of whom underwent a multi-parametric 3 Tesla MRI prior to radical prostatectomy. The prostatectomy slides were carefully co-registered to the corresponding MRI slices using an elastic registration technique. We extracted texture features from the T2-weighted imaging, pharmacokinetic features from the dynamic contrast enhanced imaging and diffusion features from the diffusion-weighted imaging for each of the confounder classes and prostate cancer. These features were selected because they form the mainstay of clinical diagnosis. Relevant features for

The confounded effects of age and exposure history in response to influenza vaccination.

PubMed

Mosterín Höpping, Ana; McElhaney, Janet; Fonville, Judith M; Powers, Douglas C; Beyer, Walter E P; Smith, Derek J

2016-01-20

Numerous studies have explored whether the antibody response to influenza vaccination in elderly adults is as strong as it is in young adults. Results vary, but tend to indicate lower post-vaccination titers (antibody levels) in the elderly, supporting the concept of immunosenescence-the weakening of the immunological response related to age. Because the elderly in such studies typically have been vaccinated against influenza before enrollment, a confounding of effects occurs between age, and previous exposures, as a potential extrinsic reason for immunosenescence. We conducted a four-year study of serial annual immunizations with inactivated trivalent influenza vaccines in 136 young adults (16 to 39 years) and 122 elderly adults (62 to 92 years). Compared to data sets of previously published studies, which were designed to investigate the effect of age, this detailed longitudinal study with multiple vaccinations allowed us to also study the effect of prior vaccination history on the response to a vaccine. In response to the first vaccination, young adults produced higher post-vaccination titers, accounting for pre-vaccination titers, than elderly adults. However, upon subsequent vaccinations the difference in response to vaccination between the young and elderly age groups declined rapidly. Although age is an important factor when modeling the outcome of the first vaccination, this term lost its relevance with successive vaccinations. In fact, when we examined the data with the assumption that the elderly group had received (on average) as few as two vaccinations prior to our study, the difference due to age disappeared. Our analyses therefore show that the initial difference between the two age groups in their response to vaccination may not be uniquely explained by immunosenescence due to ageing of the immune system, but could equally be the result of the different pre-study vaccination and infection histories in the elderly. Copyright © 2015 The Authors

Gene × environment interaction studies have not properly controlled for potential confounders: the problem and the (simple) solution.

PubMed

Keller, Matthew C

2014-01-01

Candidate gene × environment (G × E) interaction research tests the hypothesis that the effects of some environmental variable (e.g., childhood maltreatment) on some outcome measure (e.g., depression) depend on a particular genetic polymorphism. Because this research is inherently nonexperimental, investigators have been rightly concerned that detected interactions could be driven by confounders (e.g., ethnicity, gender, age, socioeconomic status) rather than by the specified genetic or environmental variables per se. In an attempt to eliminate such alternative explanations for detected G × E interactions, investigators routinely enter the potential confounders as covariates in general linear models. However, this practice does not control for the effects these variables might have on the G × E interaction. Rather, to properly control for confounders, researchers need to enter the covariate × environment and the covariate × gene interaction terms in the same model that tests the G × E term. In this manuscript, I demonstrate this point analytically and show that the practice of improperly controlling for covariates is the norm in the G × E interaction literature to date. Thus, many alternative explanations for G × E findings that investigators had thought were eliminated have not been. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

Effect of Pre-Ozonation and UF Membrane Modification with CNT on Fouling Control

NASA Astrophysics Data System (ADS)

Wang, Kailun; Guan, Yuqi; Zhu, Xuedong; Dong, Dan; Guo, Jin

2018-01-01

The effect of carbon nanotubes (CNT) modification on ultrafiltration membrane fouling control was explored. Three kinds of base membrane were chosen in the study: 20 kDa polysulfone (PS) membrane, 20 kDa and 100 kDa polyethersulfone (PES) membrane. Besides, the effect of pre-ozonation on the three CNT modified membranes for fouling alleviation was further studied. CNT modification presented antifouling properties at the beginning of filtration, while the recoverability of the CNT modified membranes are relatively lower as for the blocking of CNT layer by foulants. Pre-ozonation with a lower ozone concentration (0.25 mgO3/mgDOC) did not efficiently alleviate the fouling of CNT modified membranes. With the ozone concentration increased to 0.81 mgO3/mgDOC, the CNT modified membranes exhibited their higher antifouling properties. Water quality analysis results showed that CNT modification presented a higher capture ability for the humic-like and protein-like substances. After pre-ozonation, more organic materials could be retained in the interior of CNT layer, which decreased the fouling of base membranes and increased the permeate quality as well. Base membrane with large molecular size cut-off is more helpful for the synergistic effect of pre-ozonation and CNT modification.

Immediate effects of a distal gait modification during stair descent in individuals with patellofemoral pain.

PubMed

Aliberti, Sandra; Mezêncio, Bruno; Amadio, Alberto Carlos; Serrão, Julio Cerca; Mochizuki, Luis

2018-05-23

Knee pain during stair managing is a common complaint among individuals with PFP and can negatively affect their activities of daily living. Gait modification programs can be used to decrease patellofemoral pain. Immediate effects of a stair descent distal gait modification session that intended to emphasize forefoot landing during stair descent are described in this study. To analyze the immediate effects of a distal gait modification session on lower extremity movements and intensity of pain in women with patellofemoral pain during stair descent. Nonrandomized controlled trial. Sixteen women with patellofemoral pain were allocated into two groups: (1) Gait Modification Group (n = 8); and 2) Control Group (n = 8). The intensity of pain (visual analog scale) and kinematics of knee, ankle, and forefoot (multi-segmental foot model) during stair descent were assessed before and after the intervention. After the gait modification session, there was an increase of forefoot eversion and ankle plantarflexion as well as a decrease of knee flexion. An immediate decrease in patellofemoral pain intensity during stair descent was also observed. The distal gait modification session changed the lower extremity kinetic chain strategy of movement, increasing foot and ankle movement contribution and decreasing knee contribution to the task. An immediate decrease in patellofemoral pain intensity during stair descent was also observed. To emphasize forefoot landing may be a useful intervention to immediately relieve pain in patients with patellofemoral pain during stair descent. Clinical studies are needed to verify the gait modification session effects in medium and long terms.

Effects of Combining Na and Sr additions on Eutectic Modification in Al-Si alloy

NASA Astrophysics Data System (ADS)

Zhu, G. L.; Gu, N. J.; Zhou, B. J.

2017-09-01

Experiments were designed to investigate the effects of strontium and sodium modified on the eutectic silicon for Al-Si alloy. It was found that combining addition of Na and Sr did not appear to cause deleterious interactions of modification, at at the same time, Sr-Na was fairly constant with holding time and without obvious modification fading. Addition of Na-Sr modifier could take effect quickly and decrease incubation period.

Good research practices for comparative effectiveness research: approaches to mitigate bias and confounding in the design of nonrandomized studies of treatment effects using secondary data sources: the International Society for Pharmacoeconomics and Outcomes Research Good Research Practices for Retrospective Database Analysis Task Force Report--Part II.

PubMed

Cox, Emily; Martin, Bradley C; Van Staa, Tjeerd; Garbe, Edeltraut; Siebert, Uwe; Johnson, Michael L

2009-01-01

The goal of comparative effectiveness analysis is to examine the relationship between two variables, treatment, or exposure and effectiveness or outcome. Unlike data obtained through randomized controlled trials, researchers face greater challenges with causal inference with observational studies. Recognizing these challenges, a task force was formed to develop a guidance document on methodological approaches to addresses these biases. The task force was commissioned and a Chair was selected by the International Society for Pharmacoeconomics and Outcomes Research Board of Directors in October 2007. This report, the second of three reported in this issue of the Journal, discusses the inherent biases when using secondary data sources for comparative effectiveness analysis and provides methodological recommendations to help mitigate these biases. The task force report provides recommendations and tools for researchers to mitigate threats to validity from bias and confounding in measurement of exposure and outcome. Recommendations on design of study included: the need for data analysis plan with causal diagrams; detailed attention to classification bias in definition of exposure and clinical outcome; careful and appropriate use of restriction; extreme care to identify and control for confounding factors, including time-dependent confounding. Design of nonrandomized studies of comparative effectiveness face several daunting issues, including measurement of exposure and outcome challenged by misclassification and confounding. Use of causal diagrams and restriction are two techniques that can improve the theoretical basis for analyzing treatment effects in study populations of more homogeneity, with reduced loss of generalizability.

Use of instrumental variables in the analysis of generalized linear models in the presence of unmeasured confounding with applications to epidemiological research.

PubMed

Johnston, K M; Gustafson, P; Levy, A R; Grootendorst, P

2008-04-30

A major, often unstated, concern of researchers carrying out epidemiological studies of medical therapy is the potential impact on validity if estimates of treatment are biased due to unmeasured confounders. One technique for obtaining consistent estimates of treatment effects in the presence of unmeasured confounders is instrumental variables analysis (IVA). This technique has been well developed in the econometrics literature and is being increasingly used in epidemiological studies. However, the approach to IVA that is most commonly used in such studies is based on linear models, while many epidemiological applications make use of non-linear models, specifically generalized linear models (GLMs) such as logistic or Poisson regression. Here we present a simple method for applying IVA within the class of GLMs using the generalized method of moments approach. We explore some of the theoretical properties of the method and illustrate its use within both a simulation example and an epidemiological study where unmeasured confounding is suspected to be present. We estimate the effects of beta-blocker therapy on one-year all-cause mortality after an incident hospitalization for heart failure, in the absence of data describing disease severity, which is believed to be a confounder. 2008 John Wiley & Sons, Ltd

Drug safety analyses in a rheumatoid arthritis registry: application of different approaches regarding timing of exposure and confounder measurement.

PubMed

Solomon, Daniel H; Shadick, Nancy A; Weinblatt, Michael E; Zak, Agnes; Frits, Michelle; Franklin, Jessica M

2017-06-13

Patient registry data serves an increasing role in drug safety and comparative effectiveness research, but registry databases often do not contain confounder information measured at the same time that treatments begin. This study evaluated a set of approaches for estimating confounder values at treatment initiation using actual data from a rheumatoid arthritis (RA) registry to examine the risk of infection associated with different biologic DMARDs (bDMARDs). We examined the risk of infection associated with starting a TNF inhibitor (TNFi) versus any of the other non-TNFi bDMARDs. Different confounder assessment approaches were tested. All approaches were tested in Cox proportional hazard regression models that used a propensity score (PS). The confounder of interest was the disease activity score (DAS28-CRP). The confounder assessment approaches utilized different temporal relationships between the DAS28-CRP measurement and the start of the treatments of interest. We included 219 subjects with RA with 269 initiations of either a TNFi or a different bDMARD or both. Among this group, 305 infections were reported and confirmed through chart review. The hazard ratio (HR) for the risk of infection associated with use of a non-TNFi bDMARD ranged from 1.17 to 3.03 using 13 different approaches; only the approach with the highest HR produced results significantly different than one, but this approach included the fewest subjects and infections. The relative risk of infection for TNFi and other non-TNFi bDMARDs was similar using various approaches regarding which DAS28-CRP score should be used as the baseline measure in adjusted analyses.

Smokers' increased risk for disability pension: social confounding or health-mediated effects? Gender-specific analyses of the Hordaland Health Study cohort.

PubMed

Haukenes, Inger; Riise, Trond; Haug, Kjell; Farbu, Erlend; Maeland, John Gunnar

2013-09-01

Studies indicate that cigarette smokers have an increased risk for disability pension, presumably mediated by adverse health effects. However, smoking is also related to socioeconomic status. The current study examined the association between smoking and subsequent disability pension, and whether the association is explained by social confounding and/or health-related mediation. A subsample of 7934 men and 8488 women, aged 40-46, from the Hordaland Health Study, Norway (1997-1999), provided baseline information on smoking status, self-reported health measures and socioeconomic status. Outcome was register-based disability pension from 12 months after baseline to end of 2004. Gender stratified Cox regression analyses were used adjusted for socioeconomic status, physical activity, self-reported health and musculoskeletal pain sites. A total of 155 (2%) men and 333 (3.9%) women were granted disability pension during follow-up. The unadjusted disability risk associated with heavy smoking versus non-smoking was 1.88 (95% CI 1.23 to 2.89) among men and 3.06 (95% CI 2.23 to 4.20) among women. In multivariate analyses, adjusting for socioeconomic status, HRs were 1.33 (95% CI 0.84 to 2.11) among men and 2.22 (95% CI 1.58 to 3.13) among women. Final adjustment for physical activity, self-reported health and musculoskeletal pain further reduced the effect of heavy smoking in women (HR=1.53, 95% CI 1.09 to 2.16). Socioeconomic status confounded the smoking-related risk for disability pension; for female heavy smokers, however, a significant increased risk persisted after adjustment. Women may be particularly vulnerable to heavy smoking and to its sociomedical consequences, such as disability pension.

Comorbidities, confounders, and the white matter transcriptome in chronic alcoholism.

PubMed

Sutherland, Greg T; Sheedy, Donna; Sheahan, Pam J; Kaplan, Warren; Kril, Jillian J

2014-04-01

Alcohol abuse is the world's third leading cause of disease and disability, and one potential sequel of chronic abuse is alcohol-related brain damage (ARBD). This clinically manifests as cognitive dysfunction and pathologically as atrophy of white matter (WM) in particular. The mechanism linking chronic alcohol intoxication with ARBD remains largely unknown but it is also complicated by common comorbidities such as liver damage and nutritional deficiencies. Liver cirrhosis, in particular, often leads to hepatic encephalopathy (HE), a primary glial disease. In a novel transcriptomic study, we targeted the WM only of chronic alcoholics in an attempt to tease apart the pathogenesis of ARBD. Specifically, in alcoholics with and without HE, we explored both the prefrontal and primary motor cortices, 2 regions that experience differential levels of neuronal loss. Our results suggest that HE, along with 2 confounders, gray matter contamination, and low RNA quality are major drivers of gene expression in ARBD. All 3 exceeded the effects of alcohol itself. In particular, low-quality RNA samples were characterized by an up-regulation of translation machinery, while HE was associated with a down-regulation of mitochondrial energy metabolism pathways. The findings in HE alcoholics are consistent with the metabolic acidosis seen in this condition. In contrast non-HE alcoholics had widespread but only subtle changes in gene expression in their WM. Notwithstanding the latter result, this study demonstrates that significant confounders in transcriptomic studies of human postmortem brain tissue can be identified, quantified, and "removed" to reveal disease-specific signals. Copyright © 2014 by the Research Society on Alcoholism.

phMRI: methodological considerations for mitigating potential confounding factors

PubMed Central

Bourke, Julius H.; Wall, Matthew B.

2015-01-01

Pharmacological Magnetic Resonance Imaging (phMRI) is a variant of conventional MRI that adds pharmacological manipulations in order to study the effects of drugs, or uses pharmacological probes to investigate basic or applied (e.g., clinical) neuroscience questions. Issues that may confound the interpretation of results from various types of phMRI studies are briefly discussed, and a set of methodological strategies that can mitigate these problems are described. These include strategies that can be employed at every stage of investigation, from study design to interpretation of resulting data, and additional techniques suited for use with clinical populations are also featured. Pharmacological MRI is a challenging area of research that has both significant advantages and formidable difficulties, however with due consideration and use of these strategies many of the key obstacles can be overcome. PMID:25999812

Biomechanical and psychosocial exposures are independent risk factors for carpal tunnel syndrome: assessment of confounding using causal diagrams.

PubMed

Harris-Adamson, Carisa; Eisen, Ellen A; Neophytou, Andreas; Kapellusch, Jay; Garg, Arun; Hegmann, Kurt T; Thiese, Matthew S; Dale, Ann Marie; Evanoff, Bradley; Bao, Stephen; Silverstein, Barbara; Gerr, Fred; Burt, Susan; Rempel, David

2016-11-01

Between 2001 and 2010, six research groups conducted coordinated prospective studies of carpal tunnel syndrome (CTS) incidence among US workers from various industries to estimate exposure-response relationships. This analysis examined the presence and magnitude of confounding between biomechanical and workplace psychosocial factors and incidence of dominant-hand CTS. 1605 participants, without CTS at enrolment, were followed for up to 3.5 years (2471 person-years). Demographic information, medical history and workplace psychosocial stress measures were collected at baseline. Individual workplace biomechanical exposures were collected for each task and combined across the workweek using time-weighted averaging (TWA). CTS case criteria were based on symptoms and results of electrophysiological testing. HRs were estimated with Cox proportional hazard models. Confounding was assessed using causal diagrams and an empirical criterion of 10% or greater change in effect estimate magnitude. There were 109 incident CTS cases (IR=4.41/100 person-years; 6.7% cumulative incidence). The relationships between CTS and forceful repetition rate, % time forceful hand exertion and the Threshold Limit Value for Hand Activity Level (TLV-HAL) were slightly confounded by decision latitude with effect estimates being attenuated towards the null (10-14% change) after adjustment. The risk of CTS among participants reporting high job strain was attenuated towards the null by 14% after adjusting for the HAL Scale or the % time forceful hand exertions. Although attenuation of the relationships between CTS and some biomechanical and work psychosocial exposures was observed after adjusting for confounding, the magnitudes were small and confirmed biomechanical and work psychosocial exposures as independent risk factors for incident CTS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Correlations between cannabis use and IQ change in the Dunedin cohort are consistent with confounding from socioeconomic status

PubMed Central

Rogeberg, Ole

2013-01-01

Does cannabis use have substantial and permanent effects on neuropsychological functioning? Renewed and intense attention to the issue has followed recent research on the Dunedin cohort, which found a positive association between, on the one hand, adolescent-onset cannabis use and dependence and, on the other hand, a decline in IQ from childhood to adulthood [Meier et al. (2012) Proc Natl Acad Sci USA 109(40):E2657–E2664]. The association is given a causal interpretation by the authors, but existing research suggests an alternative confounding model based on time-varying effects of socioeconomic status on IQ. A simulation of the confounding model reproduces the reported associations from the Dunedin cohort, suggesting that the causal effects estimated in Meier et al. are likely to be overestimates, and that the true effect could be zero. Further analyses of the Dunedin cohort are proposed to distinguish between the competing interpretations. Although it would be too strong to say that the results have been discredited, the methodology is flawed and the causal inference drawn from the results premature. PMID:23319626

A Comprehensive Analysis of the SRS-Schwab Adult Spinal Deformity Classification and Confounding Variables: A Prospective, Non-US Cross-sectional Study in 292 Patients.

PubMed

Hallager, Dennis Winge; Hansen, Lars Valentin; Dragsted, Casper Rokkjær; Peytz, Nina; Gehrchen, Martin; Dahl, Benny

2016-05-01

Cross-sectional analyses on a consecutive, prospective cohort. To evaluate the ability of the Scoliosis Research Society (SRS)-Schwab Adult Spinal Deformity Classification to group patients by widely used health-related quality-of-life (HRQOL) scores and examine possible confounding variables. The SRS-Schwab Adult Spinal Deformity Classification includes sagittal modifiers considered important for HRQOL and the clinical impact of the classification has been validated in patients from the International Spine Study Group database; however, equivocal results were reported for the Pelvic Tilt modifier and potential confounding variables were not evaluated. Between March 2013 and May 2014, all adult spinal deformity patients from our outpatient clinic with sufficient radiographs were prospectively enrolled. Analyses of HRQOL variance and post hoc analyses were performed for each SRS-Schwab modifier. Age, history of spine surgery, and aetiology of spinal deformity were considered potential confounders and their influence on the association between SRS-Schwab modifiers and aggregated Oswestry Disability Index (ODI) scores was evaluated with multivariate proportional odds regressions. P values were adjusted for multiple testing. Two hundred ninety-two of 460 eligible patients were included for analyses. The SRS-Schwab Classification significantly discriminated HRQOL scores between normal and abnormal sagittal modifier classifications. Individual grade comparisons showed equivocal results; however, Pelvic Tilt grade + versus +  + did not discriminate patients according to any HRQOL score. All modifiers showed significant proportional odds for worse aggregated ODI scores with increasing grade levels and the effects were robust to confounding. However, age group and aetiology had individual significant effects. The SRS-Schwab sagittal modifiers reliably grouped patients graded 0 versus + / +  + according to the most widely used HRQOL scores and the

Evaluating the Cost-Effectiveness of Lifestyle Modification versus Metformin Therapy for the Prevention of Diabetes in Singapore

PubMed Central

Png, May Ee; Yoong, Joanne Su-Yin

2014-01-01

Background In Singapore, as diabetes is an increasingly important public health issue, the cost-effectiveness of pursuing lifestyle modification programs and/or alternative prevention strategies is of critical importance for policymakers. While the US Diabetes Prevention Program (DPP) compared weight loss through lifestyle modification with oral treatment of diabetes drug metformin to prevent/delay the onset of type 2 diabetes in pre-diabetic subjects, no data on either the actual or potential cost effectiveness of such a program is available for East or South-east Asian populations. This study estimates the 3-year cost-effectiveness of lifestyle modification and metformin among pre-diabetic subjects from a Singapore health system and societal perspective. Methodology Cost effectiveness was analysed from 2010–2012 using a decision-based model to estimate the rates of getting diabetes, healthcare costs and health-related quality of life. Cost per quality-adjusted life year (QALY) was estimated using costs relevant to the time horizon of the study from Singapore. All costs are expressed in 2012 US dollars. Principal Findings The total economic cost for non-diabetic subjects from the societal perspective was US$25,867, US$28,108 and US$26,177 for placebo, lifestyle modification and metformin intervention respectively. For diabetic patients, the total economic cost from the societal perspective was US$32,921, US$35,163 and US$33,232 for placebo, lifestyle modification and metformin intervention respectively. Lifestyle modification relative to placebo is likely to be associated with an incremental cost per QALY gained at US$36,663 while that of metformin intervention is likely to be US$6,367 from a societal perspective. Conclusion Based on adaptation of the DPP data to local conditions, both lifestyle modification and metformin intervention are likely to be cost-effective and worth implementing in Singapore to prevent or delay the onset of type 2 diabetes. However

Confounding by dietary pattern of the inverse association between alcohol consumption and type 2 diabetes risk

USDA-ARS?s Scientific Manuscript database

Epidemiology of dietary components and disease risk limits interpretability due to potential residual confounding by correlated dietary components. Dietary pattern analyses by factor analysis or partial least squares may overcome the limitation. To examine confounding by dietary pattern as well as ...

Confounding by dietary patterns of the inverse association between alcohol consumption and type 2 diabetes risk

USDA-ARS?s Scientific Manuscript database

Epidemiology of dietary components and disease risk limits interpretability due to potential residual confounding by correlated dietary components. Dietary pattern analyses by factor analysis or partial least squares may overcome this limitation. To examine confounding by dietary pattern as well as ...

Effect Of Resistance Modification On EML Capacitor Bank Performance

DTIC Science & Technology

2009-06-01

EFFECT OF RESISTANCE MODIFICATION ON EML CAPACITOR BANK PERFORMANCE* B. M. Huhman, J. M. Neri, T. L. Lockner1 Plasma Physics Division, Naval...development of an electromagnetic launcher ( EML ) for surface-fire support and other missions [1]. The Naval Research Laboratory has initiated a...develop and test materials for the study of barrel lifetime in electromagnetic launchers ( EML ) for surface-fire support and other missions [3]. The

Why does early sexual intercourse predict subsequent maladjustment? Exploring potential familial confounds.

PubMed

Donahue, Kelly L; Lichtenstein, Paul; Långström, Niklas; D'Onofrio, Brian M

2013-02-01

Previous studies have found an association between early age at first sexual intercourse and subsequent psychosocial maladjustment. Using a quasi-experimental approach, we examined the extent to which this observed association may be due to familial confounds not explored in prior research. Using a population-based cohort of Swedish adult twins (ages 19-47; N = 12,126), we examined the nature of the association between early sexual intercourse (i.e., first intercourse occurring before age 16) and various outcomes reflecting psychosocial health, including substance use, depression, criminal convictions, and adolescent childbearing. We used two methods--discordant-twin analyses and bivariate twin modeling--to estimate the extent to which genetic and environmental confounds explained observed associations. Individuals who engaged in early intercourse were at greater risk for most of the adverse psychosocial health outcomes measured in this study. However, twin pairs discordant for engaging in early intercourse did not differ significantly in their risk for psychosocial maladjustment. Our results indicated that early age at first sexual intercourse and subsequent psychosocial maladjustment may be associated because of familial factors shared by twins. Early intercourse may be associated with poor psychosocial health largely due to shared familial influences rather than through a direct causal connection. Therefore, effective and efficient interventions should address other risk factors common to early intercourse and poor psychosocial health.

Developing a Sealing Material: Effect of Epoxy Modification on Specific Physical and Mechanical Properties.

PubMed

Schoberleitner, Christoph; Archodoulaki, Vasiliki-Maria; Koch, Thomas; Lüftl, Sigrid; Werderitsch, Markus; Kuschnig, Gerhard

2013-11-27

To develop a matched sealing material for socket rehabilitation of grey cast iron pipes, an epoxy resin is modified by the addition of different components to improve the flexibility. Three different modifications are made by adding ethylene-propylene diene monomer (EPDM) rubber powder, reactive liquid polymer (ATBN) and epoxidized modifier. In this paper the effect of the modification method as well as the influence of absorption of water on the mechanical and physical properties are analyzed in terms of: tensile strength, modulus of elasticity, adhesion performance, pressure resistance, glass transition temperature and water content. A comparison with neat epoxy shows for all materials that the modulus of elasticity and strength decrease. Unlike other tested modification methods, the modification with rubber powder did not enhance the flexibility. All materials absorb water and a plasticization effect arises with further changes of mechanical and physical properties. The application of the sealant on the grey cast iron leads to a reduction of the strain at break (in comparison to the common tensile test of the pure materials) and has to be evaluated. The main requirement of pressure resistance up to 1 MPa was tested on two chosen materials. Both materials fulfill this requirement.

The Association Between Headaches and Temporomandibular Disorders is Confounded by Bruxism and Somatic Symptoms.

PubMed

van der Meer, Hedwig A; Speksnijder, Caroline M; Engelbert, Raoul H H; Lobbezoo, Frank; Nijhuis-van der Sanden, Maria W G; Visscher, Corine M

2017-09-01

The objective of this observational study was to establish the possible presence of confounders on the association between temporomandibular disorders (TMD) and headaches in a patient population from a TMD and Orofacial Pain Clinic. Several subtypes of headaches have been diagnosed: self-reported headache, (probable) migraine, (probable) tension-type headache, and secondary headache attributed to TMD. The presence of TMD was subdivided into 2 subtypes: painful TMD and function-related TMD. The associations between the subtypes of TMD and headaches were evaluated by single regression models. To study the influence of possible confounding factors on this association, the regression models were extended with age, sex, bruxism, stress, depression, and somatic symptoms. Of the included patients (n=203), 67.5% experienced headaches. In the subsample of patients with a painful TMD (n=58), the prevalence of self-reported headaches increased to 82.8%. The associations found between self-reported headache and (1) painful TMD and (2) function-related TMD were confounded by the presence of somatic symptoms. For probable migraine, both somatic symptoms and bruxism confounded the initial association found with painful TMD. The findings of this study imply that there is a central working mechanism overlapping TMD and headache. Health care providers should not regard these disorders separately, but rather look at the bigger picture to appreciate the complex nature of the diagnostic and therapeutic process.

Brief Communication: Latent toxoplasmosis and salivary testosterone concentration--important confounding factors in second to fourth digit ratio studies.

PubMed

Flegr, Jaroslav; Lindová, Jitka; Pivoñková, Vera; Havlícek, Jan

2008-12-01

A sexually dimorphic characteristic, the second to fourth digit ratio (2D:4D ratio), has been shown to reflect the prenatal concentration of sex steroid hormones and to correlate with many personality, physiological, and life history traits. The correlations are usually stronger for the right than the left hand. Most studies have shown that the 2D:4D ratio does not vary with age or postnatal concentration of sex steroid hormones. Recently, a strong association between left hand 2D:4D ratio and infection with a common human parasite Toxoplasma has been reported. We hypothesized that the confounding effect of Toxoplasma infection on left hand 2D:4D ratio could be responsible for the stronger association between different traits and right hand rather than left hand 2D:4D ratio. This confounding effect of toxoplasmosis could also be responsible for the difficulty in finding an association between 2D:4D ratio and age or postnatal steroid hormone concentration. To test this hypothesis, we analyzed the association between sex and age and 2D:4D ratio in a population of 194 female and 106 male students with and without controlling for the confounding variables of Toxoplasma infection and testosterone concentration. Our results showed that the relationship between age and sex and 2D:4D ratio increased sharply when Toxoplasma infection and testosterone concentration were controlled. These results suggest that left hand 2D:4D ratio is more susceptible to postnatal influences and that the confounding factors of Toxoplasma infection, testosterone concentration and possibly also age, should be controlled in future 2D:4D ratio studies. Because of a stronger 2D:4D dimorphism in Toxoplasma-infected than Toxoplasma-free subjects, we predict that 2D:4D ratio dimorphism as well as right hand/left hand 2D:4D ratio dimorphism will be higher in countries with a high prevalence of Toxoplasma infection than in those with a low prevalence. (c) 2008 Wiley-Liss, Inc.

A screen of chemical modifications identifies position-specific modification by UNA to most potently reduce siRNA off-target effects

PubMed Central

Bramsen, Jesper B.; Pakula, Malgorzata M.; Hansen, Thomas B.; Bus, Claus; Langkjær, Niels; Odadzic, Dalibor; Smicius, Romualdas; Wengel, Suzy L.; Chattopadhyaya, Jyoti; Engels, Joachim W.; Herdewijn, Piet; Wengel, Jesper; Kjems, Jørgen

2010-01-01

Small interfering RNAs (siRNAs) are now established as the preferred tool to inhibit gene function in mammalian cells yet trigger unintended gene silencing due to their inherent miRNA-like behavior. Such off-target effects are primarily mediated by the sequence-specific interaction between the siRNA seed regions (position 2–8 of either siRNA strand counting from the 5′-end) and complementary sequences in the 3′UTR of (off-) targets. It was previously shown that chemical modification of siRNAs can reduce off-targeting but only very few modifications have been tested leaving more to be identified. Here we developed a luciferase reporter-based assay suitable to monitor siRNA off-targeting in a high throughput manner using stable cell lines. We investigated the impact of chemically modifying single nucleotide positions within the siRNA seed on siRNA function and off-targeting using 10 different types of chemical modifications, three different target sequences and three siRNA concentrations. We found several differently modified siRNAs to exercise reduced off-targeting yet incorporation of the strongly destabilizing unlocked nucleic acid (UNA) modification into position 7 of the siRNA most potently reduced off-targeting for all tested sequences. Notably, such position-specific destabilization of siRNA–target interactions did not significantly reduce siRNA potency and is therefore well suited for future siRNA designs especially for applications in vivo where siRNA concentrations, expectedly, will be low. PMID:20453030

Determining Confounding Sensitivities In Eddy Current Thin Film Measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gros, Ethan; Udpa, Lalita; Smith, James A.

Determining Confounding Sensitivities In Eddy Current Thin Film Measurements Ethan Gros, Lalita Udpa, Electrical Engineering, Michigan State University, East Lansing MI 48824 James A. Smith, Experiment Analysis, Idaho National Laboratory, Idaho Falls ID 83415 Eddy current (EC) techniques are widely used in industry to measure the thickness of non-conductive films on a metal substrate. This is done using a system whereby a coil carrying a high-frequency alternating current is used to create an alternating magnetic field at the surface of the instrument's probe. When the probe is brought near a conductive surface, the alternating magnetic field will induce ECs inmore » the conductor. The substrate characteristics and the distance of the probe from the substrate (the coating thickness) affect the magnitude of the ECs. The induced currents load the probe coil affecting the terminal impedance of the coil. The measured probe impedance is related to the lift off between coil and conductor as well as conductivity of the test sample. For a known conductivity sample, the probe impedance can be converted into an equivalent film thickness value. The EC measurement can be confounded by a number of measurement parameters. It is the goal of this research to determine which physical properties of the measurement set-up and sample can adversely affect the thickness measurement. The eddy current testing is performed using a commercially available, hand held eddy current probe (ETA3.3H spring loaded eddy probe running at 8 MHz) that comes with a stand to hold the probe. The stand holds the probe and adjusts the probe on the z-axis to help position the probe in the correct area as well as make precise measurements. The signal from the probe is sent to a hand held readout, where the results are recorded directly in terms of liftoff or film thickness. Understanding the effect of certain factors on the measurements of film thickness, will help to evaluate how accurate the ETA3.3H

Estimating the monetary value of willingness to pay for E-book reader's attributes using partially confounded factorial conjoint choice experiment

NASA Astrophysics Data System (ADS)

Yong, Chin-Khian

2013-09-01

A partially confounded factorial conjoint choice experiments design was used to examine the monetary value of the willingness to pay for E-book Reader's attributes. Conjoint analysis is an efficient, cost-effective, and most widely used quantitative method in marketing research to understand consumer preferences and value trade-off. Value can be interpreted by customer or consumer as the received of multiple benefits from a price that was paid. The monetary value of willingness to pay for battery life, internal memory, external memory, screen size, text to Speech, touch screen, and converting handwriting to digital text of E-book reader were estimated in this study. Due to the significant interaction effect of the attributes with the price, the monetary values for the seven attributes were found to be different at different values of odds of purchasing versus not purchasing. The significant interactions effects were one of the main contribution of the partially confounded factorial conjoint choice experiment.

Indoor biofuel air pollution and respiratory health: the role of confounding factors among women in highland Guatemala.

PubMed

Bruce, N; Neufeld, L; Boy, E; West, C

1998-06-01

A number of studies have reported associations between indoor biofuel air pollution in developing countries and chronic obstructive lung disease (COLD) in adults and acute lower respiratory infection (ALRI) in children. Most of these studies have used indirect measures of exposure and generally dealt inadequately with confounding. More reliable, quantified information about this presumed effect is an important pre-requisite for prevention, not least because of the technical, economic and cultural barriers to achieving substantial exposure reductions in the world's poorest households, where ambient pollution levels are typically between ten and a hundred times higher than recommended standards. This study was carried out as part of a programme of research designed to inform the development of intervention studies capable of providing quantified estimates of health benefits. The association between respiratory symptoms and the use of open fires and chimney woodstoves ('planchas'), and the distribution of confounding factors, were examined in a cross-sectional study of 340 women aged 15-45 years, living in a poor rural area in the western highlands of Guatemala. The prevalence of reported cough and phlegm was significantly higher for three of six symptom measures among women using open fires. Although this finding is consistent with a number of other studies, none has systematically examined the extent to which strong associations with confounding variables in these settings limit the ability of observational studies to define the effect of indoor air pollution adequately. Very strong associations (P < 0.0001) were found between the type of fire and a number of household and socioeconomic factors including the arrangement of rooms, floor type, and possession of a radio and television. The spouse's economic activity type was also significantly associated (P < 0.05). Thus, while 82% of open fire users had dirt floors and only 18% cement or tile floors, the situation was

Statin adherence and risk of acute cardiovascular events among women: a cohort study accounting for time-dependent confounding affected by previous adherence.

PubMed

Lavikainen, Piia; Helin-Salmivaara, Arja; Eerola, Mervi; Fang, Gang; Hartikainen, Juha; Huupponen, Risto; Korhonen, Maarit Jaana

2016-06-03

Previous studies on the effect of statin adherence on cardiovascular events in the primary prevention of cardiovascular disease have adjusted for time-dependent confounding, but potentially introduced bias into their estimates as adherence and confounders were measured simultaneously. We aimed to evaluate the effect when accounting for time-dependent confounding affected by previous adherence as well as time sequence between factors. Retrospective cohort study. Finnish healthcare registers. Women aged 45-64 years initiating statin use for primary prevention of cardiovascular disease in 2001-2004 (n=42 807). Acute cardiovascular event defined as a composite of acute coronary syndrome and acute ischaemic stroke was our primary outcome. Low-energy fractures were used as a negative control outcome to evaluate the healthy-adherer effect. During the 3-year follow-up, 474 women experienced the primary outcome event and 557 suffered a low-energy fracture. The causal HR estimated with marginal structural model for acute cardiovascular events for all the women who remained adherent (proportion of days covered ≥80%) to statin therapy during the previous adherence assessment year was 0.78 (95% CI: 0.65 to 0.94) when compared with everybody remaining non-adherent (proportion of days covered <80%). The result was robust against alternative model specifications. Statin adherers had a potentially reduced risk of experiencing low-energy fractures compared with non-adherers (HR 0.90, 95% CI 0.76 to 1.07). Our study, which took into account the time dependence of adherence and confounders, as well as temporal order between these factors, is support for the concept that adherence to statins in women in primary prevention decreases the risk of acute cardiovascular events by about one-fifth in comparison to non-adherence. However, part of the observed effect of statin adherence on acute cardiovascular events may be due to the healthy-adherer effect. Published by the BMJ Publishing

Homophily and Contagion Are Generically Confounded in Observational Social Network Studies

PubMed Central

Shalizi, Cosma Rohilla; Thomas, Andrew C.

2012-01-01

The authors consider processes on social networks that can potentially involve three factors: homophily, or the formation of social ties due to matching individual traits; social contagion, also known as social influence; and the causal effect of an individual’s covariates on his or her behavior or other measurable responses. The authors show that generically, all of these are confounded with each other. Distinguishing them from one another requires strong assumptions on the parametrization of the social process or on the adequacy of the covariates used (or both). In particular the authors demonstrate, with simple examples, that asymmetries in regression coefficients cannot identify causal effects and that very simple models of imitation (a form of social contagion) can produce substantial correlations between an individual’s enduring traits and his or her choices, even when there is no intrinsic affinity between them. The authors also suggest some possible constructive responses to these results. PMID:22523436

Developing a Sealing Material: Effect of Epoxy Modification on Specific Physical and Mechanical Properties

PubMed Central

Schoberleitner, Christoph; Archodoulaki, Vasiliki-Maria; Koch, Thomas; Lüftl, Sigrid; Werderitsch, Markus; Kuschnig, Gerhard

2013-01-01

To develop a matched sealing material for socket rehabilitation of grey cast iron pipes, an epoxy resin is modified by the addition of different components to improve the flexibility. Three different modifications are made by adding ethylene-propylene diene monomer (EPDM) rubber powder, reactive liquid polymer (ATBN) and epoxidized modifier. In this paper the effect of the modification method as well as the influence of absorption of water on the mechanical and physical properties are analyzed in terms of: tensile strength, modulus of elasticity, adhesion performance, pressure resistance, glass transition temperature and water content. A comparison with neat epoxy shows for all materials that the modulus of elasticity and strength decrease. Unlike other tested modification methods, the modification with rubber powder did not enhance the flexibility. All materials absorb water and a plasticization effect arises with further changes of mechanical and physical properties. The application of the sealant on the grey cast iron leads to a reduction of the strain at break (in comparison to the common tensile test of the pure materials) and has to be evaluated. The main requirement of pressure resistance up to 1 MPa was tested on two chosen materials. Both materials fulfill this requirement. PMID:28788404

Adjusting for Confounding in Early Postlaunch Settings: Going Beyond Logistic Regression Models.

PubMed

Schmidt, Amand F; Klungel, Olaf H; Groenwold, Rolf H H

2016-01-01

Postlaunch data on medical treatments can be analyzed to explore adverse events or relative effectiveness in real-life settings. These analyses are often complicated by the number of potential confounders and the possibility of model misspecification. We conducted a simulation study to compare the performance of logistic regression, propensity score, disease risk score, and stabilized inverse probability weighting methods to adjust for confounding. Model misspecification was induced in the independent derivation dataset. We evaluated performance using relative bias confidence interval coverage of the true effect, among other metrics. At low events per coefficient (1.0 and 0.5), the logistic regression estimates had a large relative bias (greater than -100%). Bias of the disease risk score estimates was at most 13.48% and 18.83%. For the propensity score model, this was 8.74% and >100%, respectively. At events per coefficient of 1.0 and 0.5, inverse probability weighting frequently failed or reduced to a crude regression, resulting in biases of -8.49% and 24.55%. Coverage of logistic regression estimates became less than the nominal level at events per coefficient ≤5. For the disease risk score, inverse probability weighting, and propensity score, coverage became less than nominal at events per coefficient ≤2.5, ≤1.0, and ≤1.0, respectively. Bias of misspecified disease risk score models was 16.55%. In settings with low events/exposed subjects per coefficient, disease risk score methods can be useful alternatives to logistic regression models, especially when propensity score models cannot be used. Despite better performance of disease risk score methods than logistic regression and propensity score models in small events per coefficient settings, bias, and coverage still deviated from nominal.

Effects of Bias Modification Training in Binge Eating Disorder.

PubMed

Schmitz, Florian; Svaldi, Jennifer

2017-09-01

Food-related attentional biases have been identified as maintaining factors in binge eating disorder (BED) as they can trigger a binge episode. Bias modification training may reduce symptoms, as it has been shown to be successful in other appetitive disorders. The aim of this study was to assess and modify food-related biases in BED. It was tested whether biases could be increased and decreased by means of a modified dot-probe paradigm, how long such bias modification persisted, and whether this affected subjective food craving. Participants were randomly assigned to a bias enhancement (attend to food stimulus) group or to a bias reduction (avoid food stimulus) group. Food-related attentional bias was found to be successfully reduced in the bias-reduction group, and effects persisted briefly. Additionally, subjective craving for food was influenced by the intervention, and possible mechanisms are discussed. Given these promising initial results, future research should investigate boundary conditions of the experimental intervention to understand how it could complement treatment of BED. Copyright © 2017. Published by Elsevier Ltd.

Effects of a Read-Aloud Modification on a Standardized Reading Test

ERIC Educational Resources Information Center

Crawford, Lindy; Tindal, Gerald

2004-01-01

Researchers investigated the effects of a read-aloud modification on students' performance on a reading comprehension test. A total of 338 students in Grades 4 and 5 participated; 76 of these students (22%) received special education services, the majority of whom were labeled learning disabled. Students completed a standardized reading…

Effects of early cat or dog ownership on sensitisation and asthma in a high-risk cohort without disease-related modification of exposure.

PubMed

Almqvist, Catarina; Garden, Frances; Kemp, Andrew S; Li, Qiang; Crisafulli, Daniel; Tovey, Euan R; Xuan, Wei; Marks, Guy B

2010-03-01

Variation in the observed association between pet ownership and allergic disease may be attributable to selection bias and confounding. The aim of this study was to suggest a method to assess disease-related modification of exposure and second to examine how cat acquisition or dog ownership in early life affects atopy and asthma at 5 years. Information on sociodemographic factors and cat and dog ownership was collected longitudinally in an initially cat-free Australian birth cohort based on children with a family history of asthma. At age 5 years, 516 children were assessed for wheezing, and 488 for sensitisation. Data showed that by age 5 years, 82 children had acquired a cat. Early manifestations of allergic disease did not foreshadow a reduced rate of subsequent acquisition of a cat. Independent risk factors for acquiring a cat were exposure to tobacco smoke at home odds ratio (OR) 1.92 [95% confidence interval (CI) 1.13, 3.26], maternal education < or =12 years OR 1.95 [1.08, 3.51] and dog ownership OR 2.23 [1.23, 4.05]. Cat or dog exposure in the first 5 years was associated with a decreased risk of any allergen sensitisation, OR 0.50 [0.28, 0.88] but no association with wheeze OR 0.96 [0.57, 1.61]. This risk was not affected by age at which the cat was acquired or whether the pet was kept in- or outdoors. In conclusion, cat or dog ownership reduced the risk of subsequent atopy in this high-risk birth cohort. This cannot be explained by disease-related modification of exposure. Public health recommendations on the effect of cat and dog ownership should be based on birth cohort studies where possible selection bias has been taken into account.

LD Score Regression Distinguishes Confounding from Polygenicity in Genome-Wide Association Studies

PubMed Central

Bulik-Sullivan, Brendan K.; Loh, Po-Ru; Finucane, Hilary; Ripke, Stephan; Yang, Jian; Patterson, Nick; Daly, Mark J.; Price, Alkes L.; Neale, Benjamin M.

2015-01-01

Both polygenicity (i.e., many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from true polygenic signal and bias. We have developed an approach, LD Score regression, that quantifies the contribution of each by examining the relationship between test statistics and linkage disequilibrium (LD). The LD Score regression intercept can be used to estimate a more powerful and accurate correction factor than genomic control. We find strong evidence that polygenicity accounts for the majority of test statistic inflation in many GWAS of large sample size. PMID:25642630

Quantification of confounding factors in MRI-based dose calculations as applied to prostate IMRT

NASA Astrophysics Data System (ADS)

Maspero, Matteo; Seevinck, Peter R.; Schubert, Gerald; Hoesl, Michaela A. U.; van Asselen, Bram; Viergever, Max A.; Lagendijk, Jan J. W.; Meijer, Gert J.; van den Berg, Cornelis A. T.

2017-02-01

Magnetic resonance (MR)-only radiotherapy treatment planning requires pseudo-CT (pCT) images to enable MR-based dose calculations. To verify the accuracy of MR-based dose calculations, institutions interested in introducing MR-only planning will have to compare pCT-based and computer tomography (CT)-based dose calculations. However, interpreting such comparison studies may be challenging, since potential differences arise from a range of confounding factors which are not necessarily specific to MR-only planning. Therefore, the aim of this study is to identify and quantify the contribution of factors confounding dosimetric accuracy estimation in comparison studies between CT and pCT. The following factors were distinguished: set-up and positioning differences between imaging sessions, MR-related geometric inaccuracy, pCT generation, use of specific calibration curves to convert pCT into electron density information, and registration errors. The study comprised fourteen prostate cancer patients who underwent CT/MRI-based treatment planning. To enable pCT generation, a commercial solution (MRCAT, Philips Healthcare, Vantaa, Finland) was adopted. IMRT plans were calculated on CT (gold standard) and pCTs. Dose difference maps in a high dose region (CTV) and in the body volume were evaluated, and the contribution to dose errors of possible confounding factors was individually quantified. We found that the largest confounding factor leading to dose difference was the use of different calibration curves to convert pCT and CT into electron density (0.7%). The second largest factor was the pCT generation which resulted in pCT stratified into a fixed number of tissue classes (0.16%). Inter-scan differences due to patient repositioning, MR-related geometric inaccuracy, and registration errors did not significantly contribute to dose differences (0.01%). The proposed approach successfully identified and quantified the factors confounding accurate MRI-based dose calculation in

The effectiveness of workplace dietary modification interventions: a systematic review.

PubMed

Geaney, F; Kelly, C; Greiner, B A; Harrington, J M; Perry, I J; Beirne, P

2013-11-01

To evaluate the effectiveness of workplace dietary modification interventions alone or in combination with nutrition education on employees' dietary behaviour, health status, self-efficacy, perceived health, determinants of food choice, nutrition knowledge, co-worker support, job satisfaction, economic cost and food-purchasing patterns. Data sources included PubMed, Medline, Embase, Psych Info., Web of Knowledge and Cochrane Library (November 2011). This review was guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Studies were randomised controlled trials and controlled studies. Interventions were implemented for at least three months. Cochrane Collaboration's risk of bias tool measured potential biases. Heterogeneity precluded meta-analysis. Results were presented in a narrative summary. Six studies conducted in Brazil, the USA, Netherlands and Belgium met the inclusion criteria. Four studies reported small increases in fruit and vegetable consumption (≤half serving/day). These studies involved workplace dietary modifications and three incorporated nutrition education. Other outcomes reported included health status, co-worker support, job satisfaction, perceived health, self-efficacy and food-purchasing patterns. All studies had methodological limitations that weakened confidence in the results. Limited evidence suggests that workplace dietary modification interventions alone and in combination with nutrition education increase fruit and vegetable intakes. These interventions should be developed with recommended guidelines, workplace characteristics, long-term follow-up and objective outcomes for diet, health and cost. © 2013.

Modification of Sr on 4004 Aluminum Alloy

NASA Astrophysics Data System (ADS)

Guo, Erjun; Cao, Guojian; Feng, Yicheng; Wang, Liping; Wang, Guojun; Lv, Xinyu

2013-05-01

As a brazing foil, 4004 Al alloy has good welding performance. However, the high Si content decreases the plasticity of the alloy. To improve the plasticity of 4004 Al alloy and subsequently improve the productivity of 4004 Al foil or 434 composite foil, 4004 Al alloy was modified by Al-10%Sr master alloy. Modification effects of an additional amount of Sr, modification temperature, and holding time on 4004 aluminum alloy were studied by orthogonal design. The results showed that the greatest impact parameter of 4004 aluminum alloy modification was the additional amount of Sr, followed by holding time and modification temperature. The optimum modification parameters obtained by orthogonal design were as follows: Sr addition of 0.04%, holding time of 60 min, and modification temperature of 760°C. The effect of Sr addition on modification was analyzed in detail based on orthogonal results. With increasing of Sr addition, elongation of 4004 alloy increased at first, and decreased after reaching the maximum value.

Coping with confounds in multivoxel pattern analysis: what should we do about reaction time differences? A comment on Todd, Nystrom & Cohen 2013.

PubMed

Woolgar, Alexandra; Golland, Polina; Bode, Stefan

2014-09-01

Multivoxel pattern analysis (MVPA) is a sensitive and increasingly popular method for examining differences between neural activation patterns that cannot be detected using classical mass-univariate analysis. Recently, Todd et al. ("Confounds in multivariate pattern analysis: Theory and rule representation case study", 2013, NeuroImage 77: 157-165) highlighted a potential problem for these methods: high sensitivity to confounds at the level of individual participants due to the use of directionless summary statistics. Unlike traditional mass-univariate analyses where confounding activation differences in opposite directions tend to approximately average out at group level, group level MVPA results may be driven by any activation differences that can be discriminated in individual participants. In Todd et al.'s empirical data, factoring out differences in reaction time (RT) reduced a classifier's ability to distinguish patterns of activation pertaining to two task rules. This raises two significant questions for the field: to what extent have previous multivoxel discriminations in the literature been driven by RT differences, and by what methods should future studies take RT and other confounds into account? We build on the work of Todd et al. and compare two different approaches to remove the effect of RT in MVPA. We show that in our empirical data, in contrast to that of Todd et al., the effect of RT on rule decoding is negligible, and results were not affected by the specific details of RT modelling. We discuss the meaning of and sensitivity for confounds in traditional and multivoxel approaches to fMRI analysis. We observe that the increased sensitivity of MVPA comes at a price of reduced specificity, meaning that these methods in particular call for careful consideration of what differs between our conditions of interest. We conclude that the additional complexity of the experimental design, analysis and interpretation needed for MVPA is still not a reason to

Association between obesity and glomerular hyperfiltration: the confounding effect of smoking and sodium and protein intakes.

PubMed

Ogna, Adam; Forni Ogna, Valentina; Bochud, Murielle; Guessous, Idris; Paccaud, Fred; Burnier, Michel; Wuerzner, Gregoire

2016-04-01

Glomerular hyperfiltration has been suggested as a possible mechanism linking obesity and chronic kidney disease (CKD), independently of classical risk factors. We explored the association of overweight and obesity with glomerular hyperfiltration in a large sample of the Swiss adult population, accounting for several confounders including dietary factors. Data from a 2010 to 2012 cross-sectional population-based survey in Switzerland were used. Creatinine clearance (CrCl) was determined from 24-h urine collection; CrCl > 140 ml/min was used to define glomerular hyperfiltration. Participants were categorized into lean (<25 kg/m(2)), overweight (25-29.9 kg/m(2)) and obese (≥30 kg/m(2)) according to body mass index (BMI). A total of 1339 participants were included in the analysis [median (IQR) age 49.4 (34.3-63.5) years, 48.9 % men]. The prevalences of overweight and obesity were 32.2 and 14.2 %, respectively. Median CrCl was 102[84-121] ml/min in lean, 110 [87-136] ml/min in overweight and 124 [97-150] ml/min in obese participants (p < 0.001). The prevalence of glomerular hyperfiltration increased across BMI categories (10.4, 20.8 and 34.7 %, respectively; p < 0.001). This positive association remained significant after adjusting for age, sex, hypertension, diabetes, smoking and dietary factors (sodium and protein intakes): odds ratio [95 %CI] 2.39 [1.52-3.76] (p < 0.001) for overweight versus lean and 4.10[2.31-7.27] (p < 0.001) for obesity versus lean. BMI categories and glomerular hyperfiltration are positively associated, independently of other known CKD risk factors and dietary confounders, suggesting that glomerular hyperfiltration may represent an early renal phenotype in obesity. Our observations confirm the significant association of glomerular hyperfiltration with sodium and protein intakes and identify sodium intake as an important modifying factor of the association between hyperfiltration and obesity.

Effect of confounding variables on hemodynamic response function estimation using averaging and deconvolution analysis: An event-related NIRS study.

PubMed

Aarabi, Ardalan; Osharina, Victoria; Wallois, Fabrice

2017-07-15

Slow and rapid event-related designs are used in fMRI and functional near-infrared spectroscopy (fNIRS) experiments to temporally characterize the brain hemodynamic response to discrete events. Conventional averaging (CA) and the deconvolution method (DM) are the two techniques commonly used to estimate the Hemodynamic Response Function (HRF) profile in event-related designs. In this study, we conducted a series of simulations using synthetic and real NIRS data to examine the effect of the main confounding factors, including event sequence timing parameters, different types of noise, signal-to-noise ratio (SNR), temporal autocorrelation and temporal filtering on the performance of these techniques in slow and rapid event-related designs. We also compared systematic errors in the estimates of the fitted HRF amplitude, latency and duration for both techniques. We further compared the performance of deconvolution methods based on Finite Impulse Response (FIR) basis functions and gamma basis sets. Our results demonstrate that DM was much less sensitive to confounding factors than CA. Event timing was the main parameter largely affecting the accuracy of CA. In slow event-related designs, deconvolution methods provided similar results to those obtained by CA. In rapid event-related designs, our results showed that DM outperformed CA for all SNR, especially above -5 dB regardless of the event sequence timing and the dynamics of background NIRS activity. Our results also show that periodic low-frequency systemic hemodynamic fluctuations as well as phase-locked noise can markedly obscure hemodynamic evoked responses. Temporal autocorrelation also affected the performance of both techniques by inducing distortions in the time profile of the estimated hemodynamic response with inflated t-statistics, especially at low SNRs. We also found that high-pass temporal filtering could substantially affect the performance of both techniques by removing the low-frequency components of

Structual Effects of Cytidine 2^' Ribose Modifications as Determined by Irmpd Action Spectroscopy

NASA Astrophysics Data System (ADS)

Hamlow, Lucas; He, Chenchen; Fan, Lin; Wu, Ranran; Yang, Bo; Rodgers, M. T.; Berden, Giel; Oomens, J.

2015-06-01

Modified nucleosides, both naturally occurring and synthetic play an important role in understanding and manipulating RNA and DNA. Naturally occurring modified nucleosides are commonly found in functionally important regions of RNA and also affect antibiotic resistance or sensitivity. Synthetic modifications of nucleosides such as fluorinated and arabinosyl nucleosides have found uses as anti-virals and chemotherapy agents. Understanding the effect that modifications have on structure and glycosidic bond stability may lend insight into the functions of these modified nucleosides. Modifications such as the naturally occurring 2^'-O-methylation and the synthetic 2^'-fluorination are believed to help stabilize the nucleoside through the glycosidic bond stability and intramolecular hydrogen bonding. Changing the sugar from ribose to arabinose alters the stereochemistry at the 2^' position and thus shifts the 3D orientation of the 2^'-hydroxyl group, which also affects intramolecular hydrogen bonding and glycosidic bond stability. The structures of 2^'-deoxy-2^'-fluorocytidine, 2^'-O-methylcytidine and cytosine arabinoside are examined in the current work by measuring the infrared spectra in the IR fingerprint region using infrared multiple photon dissociation (IRMPD) action spectroscopy. The structures accessed in the experiments were determined via comparison of the measured IRMPD action spectra to the theoretical linear IR spectra determined by density functional theory and molecular modeling for the stable low-energy structures. Although glycosidic bond stability cannot be quantitatively determined from this data, complementary TCID studies will establish the effect of these modifications. Comparison of these modified nucleosides with their RNA and DNA analogues will help elucidate differences in their intrinsic chemistry.

Use of Self-Matching to Control for Stable Patient Characteristics While Addressing Time-Varying Confounding on Treatment Effect: A Case Study of Older Intensive Care Patients.

PubMed

Han, Ling; Pisani, M A; Araujo, K L B; Allore, Heather G

Exposure-crossover design offers a non-experimental option to control for stable baseline confounding through self-matching while examining causal effect of an exposure on an acute outcome. This study extends this approach to longitudinal data with repeated measures of exposure and outcome using data from a cohort of 340 older medical patients in an intensive care unit (ICU). The analytic sample included 92 patients who received ≥1 dose of haloperidol, an antipsychotic medication often used for patients with delirium. Exposure-crossover design was implemented by sampling the 3-day time segments prior ( Induction) and posterior ( Subsequent) to each treatment episode of receiving haloperidol. In the full cohort, there was a trend of increasing delirium severity scores (Mean±SD: 4.4±1.7) over the course of the ICU stay. After exposure-crossover sampling, the delirium severity score decreased from the Induction (4.9) to the Subsequent (4.1) intervals, with the treatment episode falling in-between (4.5). Based on a GEE Poisson model accounting for self-matching and within-subject correlation, the unadjusted mean delirium severity scores was -0.55 (95% CI: -1.10, -0.01) points lower for the Subsequent than the Induction intervals. The association diminished by 32% (-0.38, 95%CI: -0.99, 0.24) after adjusting only for ICU confounding, while being slightly increased by 7% (-0.60, 95%CI: -1.15, -0.04) when adjusting only for baseline characteristics. These results suggest that longitudinal exposure-crossover design is feasible and capable of partially removing stable baseline confounding through self-matching. Loss of power due to eliminating treatment-irrelevant person-time and uncertainty around allocating person-time to comparison intervals remain methodological challenges.

Data-driven confounder selection via Markov and Bayesian networks.

PubMed

Häggström, Jenny

2018-06-01

To unbiasedly estimate a causal effect on an outcome unconfoundedness is often assumed. If there is sufficient knowledge on the underlying causal structure then existing confounder selection criteria can be used to select subsets of the observed pretreatment covariates, X, sufficient for unconfoundedness, if such subsets exist. Here, estimation of these target subsets is considered when the underlying causal structure is unknown. The proposed method is to model the causal structure by a probabilistic graphical model, for example, a Markov or Bayesian network, estimate this graph from observed data and select the target subsets given the estimated graph. The approach is evaluated by simulation both in a high-dimensional setting where unconfoundedness holds given X and in a setting where unconfoundedness only holds given subsets of X. Several common target subsets are investigated and the selected subsets are compared with respect to accuracy in estimating the average causal effect. The proposed method is implemented with existing software that can easily handle high-dimensional data, in terms of large samples and large number of covariates. The results from the simulation study show that, if unconfoundedness holds given X, this approach is very successful in selecting the target subsets, outperforming alternative approaches based on random forests and LASSO, and that the subset estimating the target subset containing all causes of outcome yields smallest MSE in the average causal effect estimation. © 2017, The International Biometric Society.

Experimental modification of interpretation bias about animal fear in young children: effects on cognition, avoidance behavior, anxiety vulnerability, and physiological responding.

PubMed

Lester, Kathryn J; Field, Andy P; Muris, Peter

2011-01-01

This study investigated the effects of experimentally modifying interpretation biases for children's cognitions, avoidance behavior, anxiety vulnerability, and physiological responding. Sixty-seven children (6-11 years) were randomly assigned to receive a positive or negative interpretation bias modification procedure to induce interpretation biases toward or away from threat about ambiguous situations involving Australian marsupials. Children rapidly learned to select outcomes of ambiguous situations, which were congruent with their assigned condition. Furthermore, following positive modification, children's threat biases about novel ambiguous situations significantly decreased, whereas threat biases significantly increased after negative modification. In response to a stress-evoking behavioral avoidance test, positive modification attenuated behavioral avoidance compared to negative modification. However, no significant effects of bias modification on anxiety vulnerability or physiological responses to this stress-evoking Behavioral Avoidance Task were observed.

Methodological guidelines for developing accident modification functions.

PubMed

Elvik, Rune

2015-07-01

This paper proposes methodological guidelines for developing accident modification functions. An accident modification function is a mathematical function describing systematic variation in the effects of road safety measures. The paper describes ten guidelines. An example is given of how to use the guidelines. The importance of exploratory analysis and an iterative approach in developing accident modification functions is stressed. The example shows that strict compliance with all the guidelines may be difficult, but represents a level of stringency that should be strived for. Currently the main limitations in developing accident modification functions are the small number of good evaluation studies and the often huge variation in estimates of effect. It is therefore still not possible to develop accident modification functions for very many road safety measures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of wingtip modifications on handling qualities of agricultural aircraft

NASA Technical Reports Server (NTRS)

Van Dam, C. P.

1981-01-01

The effect of wingtip modifications on the stability and control characteristics of an agricultural airplane has been studied by means of a nonplanar quasi-vortex-lattice method. The method is used to compute the changes in steady state and perturbed state lateral-directional stability and control derivatives produced by wingtip mounted winglets, vortex diffuser vanes, and tip extensions. The study shows that the combination of the excessive positive dihedral effect produced by the winglets and adverse yaw due to aileron deflection can have a detrimental effect on the roll control characteristics of the airplane. Introduction of an aileron-rudder-interconnect, and reduction of the effective dihedral by canting-in of the winglets, or addition of a lower winglet can eliminate the roll control problems.

Improving observational study estimates of treatment effects using joint modeling of selection effects and outcomes: the case of AAA repair.

PubMed

O'Malley, A James; Cotterill, Philip; Schermerhorn, Marc L; Landon, Bruce E

2011-12-01

When 2 treatment approaches are available, there are likely to be unmeasured confounders that influence choice of procedure, which complicates estimation of the causal effect of treatment on outcomes using observational data. To estimate the effect of endovascular (endo) versus open surgical (open) repair, including possible modification by institutional volume, on survival after treatment for abdominal aortic aneurysm, accounting for observed and unobserved confounding variables. Observational study of data from the Medicare program using a joint model of treatment selection and survival given treatment to estimate the effects of type of surgery and institutional volume on survival. We studied 61,414 eligible repairs of intact abdominal aortic aneurysms during 2001 to 2004. The outcome, perioperative death, is defined as in-hospital death or death within 30 days of operation. The key predictors are use of endo, transformed endo and open volume, and endo-volume interactions. There is strong evidence of nonrandom selection of treatment with potential confounding variables including institutional volume and procedure date, variables not typically adjusted for in clinical trials. The best fitting model included heterogeneous transformations of endo volume for endo cases and open volume for open cases as predictors. Consistent with our hypothesis, accounting for unmeasured selection reduced the mortality benefit of endo. The effect of endo versus open surgery varies nonlinearly with endo and open volume. Accounting for institutional experience and unmeasured selection enables better decision-making by physicians making treatment referrals, investigators evaluating treatments, and policy makers.

Effect of bentonite modification on hardness and mechanical properties of natural rubber nanocomposites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santiago, Denise Ester O.; Department of Chemical Engineering, University of the Philippines, Los Baños, College, Laguna 4031 Philippines; Pajarito, Bryan B.

The effect of sodium activation, ion-exchange with tertiary amine salt, surface treatment with non-ionic surfactant, and wet grinding of bentonite on hardness and mechanical properties of natural rubber nanocomposites (NRN) was studied using full factorial design of experiment. Results of X-ray diffraction (XRD) show increase in basal spacing d of bentonite due to modification, while attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) confirm the organic modification of bentonite. Analysis of variance (ANOVA) shows that the main effect of surface treatment increases the hardness and decreases the tensile modulus of the NRN. The surface treatment and wet grinding of bentonitemore » decrease the tensile stresses at 100, 200 and 300% strain of NRN. Sodium activation and ion-exchange negatively affect the compressive properties, while surface treatment significantly improves the compressive properties of NRN.« less

Effect of bentonite modification on hardness and mechanical properties of natural rubber nanocomposites

NASA Astrophysics Data System (ADS)

Santiago, Denise Ester O.; Pajarito, Bryan B.; Mangaccat, Winna Faye F.; Tigue, Maelyn Rose M.; Tipton, Monica T.

2016-05-01

The effect of sodium activation, ion-exchange with tertiary amine salt, surface treatment with non-ionic surfactant, and wet grinding of bentonite on hardness and mechanical properties of natural rubber nanocomposites (NRN) was studied using full factorial design of experiment. Results of X-ray diffraction (XRD) show increase in basal spacing d of bentonite due to modification, while attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) confirm the organic modification of bentonite. Analysis of variance (ANOVA) shows that the main effect of surface treatment increases the hardness and decreases the tensile modulus of the NRN. The surface treatment and wet grinding of bentonite decrease the tensile stresses at 100, 200 and 300% strain of NRN. Sodium activation and ion-exchange negatively affect the compressive properties, while surface treatment significantly improves the compressive properties of NRN.

Arnica montana experimental studies: confounders and biases?

PubMed

Bellavite, Paolo; Marzotto, Marta; Bonafini, Clara

2018-03-01

Arnica montana is a popular traditional remedy widely used in complementary and alternative medicine, in part for its wound-healing properties. The authors recently showed that this plant extract and several of its homeopathic dilutions are able to modify the expression of a series of genes involved in inflammation and connective tissue regeneration. Their studies opened a debate, including criticisms to the "errors" in the methods used and the "confounders and biases". Here the authors show that the criticisms raised on methodology and statistics are not consistent and cannot be considered pertinent. The present comment also updates and reviews information concerning the action of A. montana dilutions in human macrophage cells while summarizing the major experimental advances reported on this interesting medicinal plant. Copyright © 2018. Published by Elsevier B.V.

Demonstrating the effect of forensic firearm countermeasures: Bullet characteristics generated due to barrel modifications.

PubMed

O'Keeffe, C; Champion, S; Allsop, D

2015-12-01

Forensic awareness and the declining availability of firearms have resulted in an increase in the use of modified and re-activated firearms in crime. Although some modifications are undertaken to simply acquire a functioning firearm, others are perpetrated as a direct forensic countermeasure to prevent the association between a firearm and a crime. This article describes the effects of these modifications on bullet striation patterns imparted from the barrel to a fired bullet. The key results indicated that the investigated modifications display assessable characteristics. The use of an oversized barrel imparted striations consistent with firing with the absence of typical rifling. Subsequent or consecutively fired bullets possessed striation variations, with the first showing the least evidence of striations. The application of a choke resulted in more obvious bullet elongation compared to a smoothbore barrel. The restriction caused merging of lands and groves of the imparted rifling and obscured their usual definition. Effects of breech adaption were also characterised by observing the buckling and enlargement of the cartridge case. This deformity of the cartridge case was most evident when the barrel pressure increased due to the presence of the choke. From this study it was evident that unique characteristic impressions associated with different modifications most commonly found in criminal investigations can be utilised by a forensic expert and impart significant intelligence to an investigation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Drug induced liver injury with analysis of alternative causes as confounding variables.

PubMed

Teschke, Rolf; Danan, Gaby

2018-04-01

Drug-induced liver injury (DILI) is rare compared to the worldwide frequent acute or chronic liver diseases. Therefore, patients included in series of suspected DILI are at high risk of not having DILI, whereby alternative causes may confound the DILI diagnosis. The aim of this review is to evaluate published case series of DILI for alternative causes. Relevant studies were identified using a computerized search of the Medline database for publications from 1993 through 30 October 2017. We used the following terms: drug hepatotoxicity, drug induced liver injury, hepatotoxic drugs combined with diagnosis, causality assessment and alternative causes. Alternative causes as variables confounding the DILI diagnosis emerged in 22 published DILI case series, ranging from 4 to 47%. Among 13 335 cases of suspected DILI, alternative causes were found to be more likely in 4555 patients (34.2%), suggesting that the suspected DILI was probably not DILI. Biliary diseases such as biliary obstruction, cholangitis, choledocholithiasis, primary biliary cholangitis and primary sclerosing cholangitis were among the most missed diagnoses. Alternative causes included hepatitis B, C and E, cytomegalovirus, Epstein-Barr virus, ischemic hepatitis, cardiac hepatopathy, autoimmune hepatitis, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and alcoholic liver disease. In more than one-third of published global DILI case series, alternative causes as published in these reports confounded the DILI diagnosis. In the future, published DILI case series should include only patients with secured DILI diagnosis, preferentially established by prospective use of scored items provided by robust diagnostic algorithms such as the updated Roussel Uclaf causality assessment method. © 2018 The British Pharmacological Society.

Confounding factors in the detection of species responses to habitat fragmentation.

PubMed

Ewers, Robert M; Didham, Raphael K

2006-02-01

Habitat loss has pervasive and disruptive impacts on biodiversity in habitat remnants. The magnitude of the ecological impacts of habitat loss can be exacerbated by the spatial arrangement -- or fragmentation -- of remaining habitat. Fragmentation per se is a landscape-level phenomenon in which species that survive in habitat remnants are confronted with a modified environment of reduced area, increased isolation and novel ecological boundaries. The implications of this for individual organisms are many and varied, because species with differing life history strategies are differentially affected by habitat fragmentation. Here, we review the extensive literature on species responses to habitat fragmentation, and detail the numerous ways in which confounding factors have either masked the detection, or prevented the manifestation, of predicted fragmentation effects. Large numbers of empirical studies continue to document changes in species richness with decreasing habitat area, with positive, negative and no relationships regularly reported. The debate surrounding such widely contrasting results is beginning to be resolved by findings that the expected positive species-area relationship can be masked by matrix-derived spatial subsidies of resources to fragment-dwelling species and by the invasion of matrix-dwelling species into habitat edges. Significant advances have been made recently in our understanding of how species interactions are altered at habitat edges as a result of these changes. Interestingly, changes in biotic and abiotic parameters at edges also make ecological processes more variable than in habitat interiors. Individuals are more likely to encounter habitat edges in fragments with convoluted shapes, leading to increased turnover and variability in population size than in fragments that are compact in shape. Habitat isolation in both space and time disrupts species distribution patterns, with consequent effects on metapopulation dynamics and the

The effect of transverse flow on the nuclear modification factor at RHIC and LHC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Betz, Barbara; Gyulassy, Miklos

2016-01-22

We determine the nuclear modification factor at RHIC and LHC energies using a generic jet-energy loss model that is expanded by an additional flow factor accounting for the impact of transverse flow. We consider a pQCD-based ansatz with and without jet-energy loss fluctuations that is coupled to a state-of-the-art hydrodynamic prescription and includes a running coupling effect. We show that the nuclear modification factor is a rather insensitive quantity that is barely affected by the flow dynamics of the medium created in a heavy-ion collision.

Effects of Site-Specific Guanine C8-Modifications on an Intramolecular DNA G-Quadruplex

PubMed Central

Lech, Christopher Jacques; Cheow Lim, Joefina Kim; Wen Lim, Jocelyn Mei; Amrane, Samir; Heddi, Brahim; Phan, Anh Tuân

2011-01-01

Understanding the fundamentals of G-quadruplex formation is important both for targeting G-quadruplexes formed by natural sequences and for engineering new G-quadruplexes with desired properties. Using a combination of experimental and computational techniques, we have investigated the effects of site-specific substitution of a guanine with C8-modified guanine derivatives, including 8-bromo-guanine, 8-O-methyl-guanine, 8-amino-guanine, and 8-oxo-guanine, within a well-defined (3 + 1) human telomeric G-quadruplex platform. The effects of substitutions on the stability of the G-quadruplex were found to depend on the type and position of the modification among different guanines in the structure. An interesting modification-dependent NMR chemical-shift effect was observed across basepairing within a guanine tetrad. This effect was reproduced by ab initio quantum mechanical computations, which showed that the observed variation in imino proton chemical shift is largely influenced by changes in hydrogen-bond geometry within the guanine tetrad. PMID:22004753

The assessment of cortisol in human hair: associations with sociodemographic variables and potential confounders.

PubMed

Dettenborn, L; Tietze, A; Kirschbaum, C; Stalder, T

2012-11-01

To inform the future use of hair cortisol measurement, we have investigated influences of potential confounding variables (natural hair colour, frequency of hair washes, age, sex, oral contraceptive (OC) use and smoking status) on hair cortisol levels. The main study sample comprised 360 participants (172 women) covering a wide range of ages (1-91 years; mean = 25.95). In addition, to more closely examine influences of natural hair colour and young age on hair cortisol levels, two additional samples comprising 69 participants with natural blond or dark brown hair (hair colour sample) as well as 28 young children and 34 adults (young age sample) were recruited. Results revealed a lack of an effect for natural hair colour, OC use, and smoking status on hair cortisol levels (all p's >0.10). No influence of frequency of hair washes was seen for proximal hair segments (p = 0.335) but for the third hair segment indicating lower cortisol content (p = 0.008). We found elevated hair cortisol levels in young children and older adults (p < 0.001). Finally, men showed higher hair cortisol levels than women (p = 0.002). The present data indicate that hair cortisol measurement provides a useful tool in stress-related psychobiological research when applied with the consideration of possible confounders including age and sex.

The impact of ambient fine particles on influenza transmission and the modification effects of temperature in China: A multi-city study.

PubMed

Chen, Gongbo; Zhang, Wenyi; Li, Shanshan; Zhang, Yongming; Williams, Gail; Huxley, Rachel; Ren, Hongyan; Cao, Wei; Guo, Yuming

2017-01-01

There is good evidence that air pollution is a risk factor for adverse respiratory and vascular health outcomes. However, data are limited as to whether ambient fine particles contribute to the transmission of influenza and if so, how the association is modified by weather conditions. We examined the relationship between ambient PM 2.5 and influenza incidence at the national level in China and explored the associations at different temperatures. Daily data on concentrations of particulate matter with aerodynamic diameter<2.5μm (PM 2.5 ) and influenza incidence counts were collected in 47 Chinese cities. A Poisson regression model was used to estimate the city-specific PM 2.5 -influenza association, after controlling for potential confounders. Then, a random-effect meta-analysis was used to pool the effects at national level. In addition, stratified analyses were performed to examine modification effects of ambient temperature. For single lag models, the highest effect of ambient PM 2.5 on influenza incidence appeared at lag day 2, with relative risk (RR) of 1.015 (95% confidence interval (CI): 1.004, 1.025) associated with a 10μg/m 3 increase in PM 2.5 . For moving average lag models, the significant association was found at lag 2-3days, with RR of 1.020 (95% CI: 1.006, 1.034). The RR of influenza transmission associated with PM 2.5 was higher for cold compared with hot days. Overall, 10.7% of incident influenza cases may result from exposure to ambient PM 2.5 . Ambient PM 2.5 may increase the risk of exposure to influenza in China especially on cooler days. Control measures to reduce PM 2.5 concentrations could potentially also be of benefit in lowering the risk of exposure and subsequent transmission of influenza in China. Copyright © 2016 Elsevier Ltd. All rights reserved.

Heat waves in the United States: mortality risk during heat waves and effect modification by heat wave characteristics in 43 U.S. communities.

PubMed

Anderson, G Brooke; Bell, Michelle L

2011-02-01

Devastating health effects from recent heat waves, and projected increases in frequency, duration, and severity of heat waves from climate change, highlight the importance of understanding health consequences of heat waves. We analyzed mortality risk for heat waves in 43 U.S. cities (1987-2005) and investigated how effects relate to heat waves' intensity, duration, or timing in season. Heat waves were defined as ≥ 2 days with temperature ≥ 95th percentile for the community for 1 May through 30 September. Heat waves were characterized by their intensity, duration, and timing in season. Within each community, we estimated mortality risk during each heat wave compared with non-heat wave days, controlling for potential confounders. We combined individual heat wave effect estimates using Bayesian hierarchical modeling to generate overall effects at the community, regional, and national levels. We estimated how heat wave mortality effects were modified by heat wave characteristics (intensity, duration, timing in season). Nationally, mortality increased 3.74% [95% posterior interval (PI), 2.29-5.22%] during heat waves compared with non-heat wave days. Heat wave mortality risk increased 2.49% for every 1°F increase in heat wave intensity and 0.38% for every 1-day increase in heat wave duration. Mortality increased 5.04% (95% PI, 3.06-7.06%) during the first heat wave of the summer versus 2.65% (95% PI, 1.14-4.18%) during later heat waves, compared with non-heat wave days. Heat wave mortality impacts and effect modification by heat wave characteristics were more pronounced in the Northeast and Midwest compared with the South. We found higher mortality risk from heat waves that were more intense or longer, or those occurring earlier in summer. These findings have implications for decision makers and researchers estimating health effects from climate change.

The effects of landscape modifications on the long-term persistence of animal populations.

PubMed

Nabe-Nielsen, Jacob; Sibly, Richard M; Forchhammer, Mads C; Forbes, Valery E; Topping, Christopher J

2010-01-28

The effects of landscape modifications on the long-term persistence of wild animal populations is of crucial importance to wildlife managers and conservation biologists, but obtaining experimental evidence using real landscapes is usually impossible. To circumvent this problem we used individual-based models (IBMs) of interacting animals in experimental modifications of a real Danish landscape. The models incorporate as much as possible of the behaviour and ecology of four species with contrasting life-history characteristics: skylark (Alauda arvensis), vole (Microtus agrestis), a ground beetle (Bembidion lampros) and a linyphiid spider (Erigone atra). This allows us to quantify the population implications of experimental modifications of landscape configuration and composition. Starting with a real agricultural landscape, we progressively reduced landscape complexity by (i) homogenizing habitat patch shapes, (ii) randomizing the locations of the patches, and (iii) randomizing the size of the patches. The first two steps increased landscape fragmentation. We assessed the effects of these manipulations on the long-term persistence of animal populations by measuring equilibrium population sizes and time to recovery after disturbance. Patch rearrangement and the presence of corridors had a large effect on the population dynamics of species whose local success depends on the surrounding terrain. Landscape modifications that reduced population sizes increased recovery times in the short-dispersing species, making small populations vulnerable to increasing disturbance. The species that were most strongly affected by large disturbances fluctuated little in population sizes in years when no perturbations took place. Traditional approaches to the management and conservation of populations use either classical methods of population analysis, which fail to adequately account for the spatial configurations of landscapes, or landscape ecology, which accounts for landscape

Selection bias and patterns of confounding in cohort studies: the case of the NINFEA web-based birth cohort.

PubMed

Pizzi, Costanza; De Stavola, Bianca L; Pearce, Neil; Lazzarato, Fulvio; Ghiotti, Paola; Merletti, Franco; Richiardi, Lorenzo

2012-11-01

Several studies have examined the effects of sample selection on the exposure-outcome association estimates in cohort studies, but the reasons why this selection may induce bias have not been fully explored. To investigate how sample selection of the web-based NINFEA birth cohort may change the confounding patterns present in the source population. The characteristics of the NINFEA participants (n=1105) were compared with those of the wider source population-the Piedmont Birth Registry (PBR)-(n=36 092), and the association of two exposures (parity and educational level) with two outcomes (low birth weight and birth by caesarean section), while controlling for other risk factors, was studied. Specifically the associations among measured risk factors within each dataset were examined and the exposure-outcome estimates compared in terms of relative ORs. The associations of educational level with the other risk factors (alcohol consumption, folic acid intake, maternal age, pregnancy weight gain, previous miscarriages) partly differed between PBR and NINFEA. This was not observed for parity. Overall, the exposure-outcome estimates derived from NINFEA only differed moderately from those obtained in PBR, with relative ORs ranging between 0.74 and 1.03. Sample selection in cohort studies may alter the confounding patterns originally present in the general population. However, this does not necessarily introduce selection bias in the exposure-outcome estimates, as sample selection may reduce some of the residual confounding present in the general population.

Packet Randomized Experiments for Eliminating Classes of Confounders

PubMed Central

Pavela, Greg; Wiener, Howard; Fontaine, Kevin R.; Fields, David A.; Voss, Jameson D.; Allison, David B.

2014-01-01

Background Although randomization is considered essential for causal inference, it is often not possible to randomize in nutrition and obesity research. To address this, we develop a framework for an experimental design—packet randomized experiments (PREs), which improves causal inferences when randomization on a single treatment variable is not possible. This situation arises when subjects are randomly assigned to a condition (such as a new roommate) which varies in one characteristic of interest (such as weight), but also varies across many others. There has been no general discussion of this experimental design, including its strengths, limitations, and statistical properties. As such, researchers are left to develop and apply PREs on an ad hoc basis, limiting its potential to improve causal inferences among nutrition and obesity researchers. Methods We introduce PREs as an intermediary design between randomized controlled trials and observational studies. We review previous research that used the PRE design and describe its application in obesity-related research, including random roommate assignments, heterochronic parabiosis, and the quasi-random assignment of subjects to geographic areas. We then provide a statistical framework to control for potential packet-level confounders not accounted for by randomization. Results PREs have successfully been used to improve causal estimates of the effect of roommates, altitude, and breastfeeding on weight outcomes. When certain assumptions are met, PREs can asymptotically control for packet-level characteristics. This has the potential to statistically estimate the effect of a single treatment even when randomization to a single treatment did not occur. Conclusions Applying PREs to obesity-related research will improve decisions about clinical, public health, and policy actions insofar as it offers researchers new insight into cause and effect relationships among variables. PMID:25444088

Genetic variation of loci potentially under selection confounds species-genetic diversity correlations in a fragmented habitat.

PubMed

Bertin, Angeline; Gouin, Nicolas; Baumel, Alex; Gianoli, Ernesto; Serratosa, Juan; Osorio, Rodomiro; Manel, Stephanie

2017-01-01

Positive species-genetic diversity correlations (SGDCs) are often thought to result from the parallel influence of neutral processes on genetic and species diversity. Yet, confounding effects of non-neutral mechanisms have not been explored. Here, we investigate the impact of non-neutral genetic diversity on SGDCs in high Andean wetlands. We compare correlations between plant species diversity and genetic diversity (GD) calculated with and without loci potentially under selection (outlier loci). The study system includes 2188 specimens from five species (three common aquatic macroinvertebrate and two dominant plant species) that were genotyped for 396 amplified fragment length polymorphism loci. We also appraise the importance of neutral processes on SGDCs by investigating the influence of habitat fragmentation features. Significant positive SGDCs were detected for all five species (mean SGDC = 0.52 ± 0.05). While only a few outlier loci were detected in each species, they resulted in significant decreases in GD and in SGDCs. This supports the hypothesis that neutral processes drive species-genetic diversity relationships in high Andean wetlands. Unexpectedly, the effects on genetic diversity GD of the habitat fragmentation characteristics in this study increased with the presence of outlier loci in two species. Overall, our results reveal pitfalls in using habitat features to infer processes driving SGDCs and show that a few loci potentially under selection are enough to cause a significant downward bias in SGDC. Investigating confounding effects of outlier loci thus represents a useful approach to evidence the contribution of neutral processes on species-genetic diversity relationships. © 2016 John Wiley & Sons Ltd.

Prediction of effects of wing contour modifications on low-speed maximum lift and transonic performance for the EA-6B aircraft

NASA Technical Reports Server (NTRS)

Allison, Dennis O.; Waggoner, E. G.

1990-01-01

Computational predictions of the effects of wing contour modifications on maximum lift and transonic performance were made and verified against low speed and transonic wind tunnel data. This effort was part of a program to improve the maneuvering capability of the EA-6B electronics countermeasures aircraft, which evolved from the A-6 attack aircraft. The predictions were based on results from three computer codes which all include viscous effects: MCARF, a 2-D subsonic panel code; TAWFIVE, a transonic full potential code; and WBPPW, a transonic small disturbance potential flow code. The modifications were previously designed with the aid of these and other codes. The wing modifications consists of contour changes to the leading edge slats and trailing edge flaps and were designed for increased maximum lift with minimum effect on transonic performance. The prediction of the effects of the modifications are presented, with emphasis on verification through comparisons with wind tunnel data from the National Transonic Facility. Attention is focused on increments in low speed maximum lift and increments in transonic lift, pitching moment, and drag resulting from the contour modifications.

ADC Quantification of the Vertebral Bone Marrow Water Component: Removing the Confounding Effect of Residual Fat.

PubMed

Dieckmeyer, Michael; Ruschke, Stefan; Eggers, Holger; Kooijman, Hendrik; Rummeny, Ernst J; Kirschke, Jan S; Baum, Thomas; Karampinos, Dimitrios C

2017-10-01

To remove the confounding effect of unsuppressed fat on the imaging-based apparent diffusion coefficient (ADC) of the vertebral bone marrow water component when using spectrally selective fat suppression and to compare and validate the proposed quantification strategy against diffusion-weighted magnetic resonance spectroscopy (DW-MRS). Twelve subjects underwent diffusion-weighted imaging (DWI) and DW-MRS of the vertebral bone marrow. A theoretical model was developed to take into account and correct the effects of residual fat on ADC, incorporating additional measurements for proton density fat fraction (PDFF) and water T 2 (T 2w ). Uncorrected and corrected DWI-based ADC was compared with DW-MRS-based ADC using the Bland-Altman method. There was a systematic bias equal to 0.118 ± 0.116 × 10 -3 mm 2 /s between DWI and DW-MRS when no correction was performed. Taking into account measured PDFF and constant T 2w reduced the bias to 0.006 ± 0.128 × 10 -3 mm 2 /s. Using the proposed approach with both individually measured PDFF and T 2w reduced both the bias and the limits of agreement between DWI and DW-MRS (0.018 ± 0.065 × 10 -3 mm 2 /s). By taking into account the presence of residual fat in a modified signal model that incorporates additional individual measurements of PDFF and T 2w , good agreement of imaging-based ADC with MRS-based ADC can be achieved in vertebral bone marrow. Magn Reson Med 78:1432-1441, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Is the Relation Between Ozone and Mortality Confounded by Chemical Components of Particulate Matter? Analysis of 7 Components in 57 US Communities

PubMed Central

Anderson, G. Brooke; Krall, Jenna R.; Peng, Roger D.; Bell, Michelle L.

2012-01-01

Epidemiologic studies have linked tropospheric ozone pollution and human mortality. Although research has shown that this relation is not confounded by particulate matter when measured by mass, little scientific evidence exists on whether confounding exists by chemical components of the particle mixture. Using mortality and particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5) component data from 57 US communities (2000–2005), the authors investigate whether the ozone-mortality relation is confounded by 7 components of PM2.5: sulfate, nitrate, silicon, elemental carbon, organic carbon matter, sodium ion, and ammonium. Together, these components constitute most PM2.5 mass in the United States. Estimates of the effect of ozone on mortality were almost identical before and after controlling for the 7 components of PM2.5 considered (mortality increase/10-ppb ozone increase, before and after controlling: ammonium, 0.34% vs. 0.35%; elemental carbon, 0.36% vs. 0.37%; nitrate, 0.27% vs. 0.26%; organic carbon matter, 0.34% vs. 0.31%; silicon, 0.36% vs. 0.37%; sodium ion, 0.21% vs. 0.18%; and sulfate, 0.35% vs. 0.38%). Additionally, correlations were weak between ozone and each particulate component across all communities. Previous research found that the ozone-mortality relation is not confounded by particulate matter measured by mass; this national study indicates that the relation is also robust to control for specific components of PM2.5. PMID:23043133

Task-switching cost and repetition priming: two overlooked confounds in the first-set procedure of the Sternberg paradigm and how they affect memory set-size effects.

PubMed

Jou, Jerwen

2014-10-01

Subjects performed Sternberg-type memory recognition tasks (Sternberg paradigm) in four experiments. Category-instance names were used as learning and testing materials. Sternberg's original experiments demonstrated a linear relation between reaction time (RT) and memory-set size (MSS). A few later studies found no relation, and other studies found a nonlinear relation (logarithmic) between the two variables. These deviations were used as evidence undermining Sternberg's serial scan theory. This study identified two confounding variables in the fixed-set procedure of the paradigm (where multiple probes are presented at test for a learned memory set) that could generate a MSS RT function that was either flat or logarithmic rather than linearly increasing. These two confounding variables were task-switching cost and repetition priming. The former factor worked against smaller memory sets and in favour of larger sets whereas the latter factor worked in the opposite way. Results demonstrated that a null or a logarithmic RT-to-MSS relation could be the artefact of the combined effects of these two variables. The Sternberg paradigm has been used widely in memory research, and a thorough understanding of the subtle methodological pitfalls is crucial. It is suggested that a varied-set procedure (where only one probe is presented at test for a learned memory set) is a more contamination-free procedure for measuring the MSS effects, and that if a fixed-set procedure is used, it is worthwhile examining the RT function of the very first trials across the MSSs, which are presumably relatively free of contamination by the subsequent trials.

Seasonal and temperature modifications of the association between fine particulate air pollution and cardiovascular hospitalization in New York state.

PubMed

Hsu, Wan-Hsiang; Hwang, Syni-An; Kinney, Patrick L; Lin, Shao

2017-02-01

It is known that extreme temperature and ambient air pollution are each independently associated with human health outcomes. However, findings from the few studies that have examined modified effects by seasons and the interaction between air pollution and temperature on health endpoints are inconsistent. This study examines the effects of short-term PM 2.5 (particulate matter less than or equal to 2.5μm in aerodynamic diameter) on hospitalization for cardiovascular diseases (CVDs), its modifications by season and temperature, and whether these effects are heterogeneous across different regions in New York State (NYS). We used daily average temperature and PM 2.5 concentrations as exposure indicators and performed a time series analysis with a quasi-Poisson model, controlling for possible confounders, such as time-relevant variables and dew point, for CVDs in NYS, 1991-2006. Stratification parametric models were applied to evaluate the modifying effects by seasons and temperature. Across the whole year, a 10-μg/m 3 increment in PM 2.5 concentration accounted for a 1.37% increase in CVDs (95% confidence interval (CI): 0.90%, 1.84%) in New York City, Long Island & Hudson. The PM 2.5 effect was strongest in winter, with an additional 2.06% (95% CI: 1.33%, 2.80%) increase in CVDs observed per 10-μg/m 3 increment in PM 2.5 . Temperature modified the PM 2.5 effects on CVDs, and these modifications by temperature on PM 2.5 effects on CVDs were found at low temperature days. These associations were heterogeneous across four PM 2.5 concentration regions. PM 2.5 was positively associated with CVD hospitalizations. The short-term PM 2.5 effect varied with season and temperature levels, and stronger effects were observed in winter and at low temperature days. Copyright © 2016 Elsevier B.V. All rights reserved.

Review of methods for handling confounding by cluster and informative cluster size in clustered data

PubMed Central

Seaman, Shaun; Pavlou, Menelaos; Copas, Andrew

2014-01-01

Clustered data are common in medical research. Typically, one is interested in a regression model for the association between an outcome and covariates. Two complications that can arise when analysing clustered data are informative cluster size (ICS) and confounding by cluster (CBC). ICS and CBC mean that the outcome of a member given its covariates is associated with, respectively, the number of members in the cluster and the covariate values of other members in the cluster. Standard generalised linear mixed models for cluster-specific inference and standard generalised estimating equations for population-average inference assume, in general, the absence of ICS and CBC. Modifications of these approaches have been proposed to account for CBC or ICS. This article is a review of these methods. We express their assumptions in a common format, thus providing greater clarity about the assumptions that methods proposed for handling CBC make about ICS and vice versa, and about when different methods can be used in practice. We report relative efficiencies of methods where available, describe how methods are related, identify a previously unreported equivalence between two key methods, and propose some simple additional methods. Unnecessarily using a method that allows for ICS/CBC has an efficiency cost when ICS and CBC are absent. We review tools for identifying ICS/CBC. A strategy for analysis when CBC and ICS are suspected is demonstrated by examining the association between socio-economic deprivation and preterm neonatal death in Scotland. PMID:25087978

Multisample adjusted U-statistics that account for confounding covariates.

PubMed

Satten, Glen A; Kong, Maiying; Datta, Somnath

2018-06-19

Multisample U-statistics encompass a wide class of test statistics that allow the comparison of 2 or more distributions. U-statistics are especially powerful because they can be applied to both numeric and nonnumeric data, eg, ordinal and categorical data where a pairwise similarity or distance-like measure between categories is available. However, when comparing the distribution of a variable across 2 or more groups, observed differences may be due to confounding covariates. For example, in a case-control study, the distribution of exposure in cases may differ from that in controls entirely because of variables that are related to both exposure and case status and are distributed differently among case and control participants. We propose to use individually reweighted data (ie, using the stratification score for retrospective data or the propensity score for prospective data) to construct adjusted U-statistics that can test the equality of distributions across 2 (or more) groups in the presence of confounding covariates. Asymptotic normality of our adjusted U-statistics is established and a closed form expression of their asymptotic variance is presented. The utility of our approach is demonstrated through simulation studies, as well as in an analysis of data from a case-control study conducted among African-Americans, comparing whether the similarity in haplotypes (ie, sets of adjacent genetic loci inherited from the same parent) occurring in a case and a control participant differs from the similarity in haplotypes occurring in 2 control participants. Copyright © 2018 John Wiley & Sons, Ltd.

Potential confounding in the association between short birth intervals and increased neonatal, infant, and child mortality

PubMed Central

Perin, Jamie; Walker, Neff

2015-01-01

Background Recent steep declines in child mortality have been attributed in part to increased use of contraceptives and the resulting change in fertility behaviour, including an increase in the time between births. Previous observational studies have documented strong associations between short birth spacing and an increase in the risk of neonatal, infant, and under-five mortality, compared to births with longer preceding birth intervals. In this analysis, we compare two methods to estimate the association between short birth intervals and mortality risk to better inform modelling efforts linking family planning and mortality in children. Objectives Our goal was to estimate the mortality risk for neonates, infants, and young children by preceding birth space using household survey data, controlling for mother-level factors and to compare the results to those from previous analyses with survey data. Design We assessed the potential for confounding when estimating the relative mortality risk by preceding birth interval and estimated mortality risk by birth interval in four categories: less than 18 months, 18–23 months, 24–35 months, and 36 months or longer. We estimated the relative risks among women who were 35 and older at the time of the survey with two methods: in a Cox proportional hazards regression adjusting for potential confounders and also by stratifying Cox regression by mother, to control for all factors that remain constant over a woman's childbearing years. We estimated the overall effects for birth spacing in a meta-analysis with random survey effects. Results We identified several factors known for their associations with neonatal, infant, and child mortality that are also associated with preceding birth interval. When estimating the effect of birth spacing on mortality, we found that regression adjustment for these factors does not substantially change the risk ratio for short birth intervals compared to an unadjusted mortality ratio. For birth

Potential confounding in the association between short birth intervals and increased neonatal, infant, and child mortality.

PubMed

Perin, Jamie; Walker, Neff

2015-01-01

Recent steep declines in child mortality have been attributed in part to increased use of contraceptives and the resulting change in fertility behaviour, including an increase in the time between births. Previous observational studies have documented strong associations between short birth spacing and an increase in the risk of neonatal, infant, and under-five mortality, compared to births with longer preceding birth intervals. In this analysis, we compare two methods to estimate the association between short birth intervals and mortality risk to better inform modelling efforts linking family planning and mortality in children. Our goal was to estimate the mortality risk for neonates, infants, and young children by preceding birth space using household survey data, controlling for mother-level factors and to compare the results to those from previous analyses with survey data. We assessed the potential for confounding when estimating the relative mortality risk by preceding birth interval and estimated mortality risk by birth interval in four categories: less than 18 months, 18-23 months, 24-35 months, and 36 months or longer. We estimated the relative risks among women who were 35 and older at the time of the survey with two methods: in a Cox proportional hazards regression adjusting for potential confounders and also by stratifying Cox regression by mother, to control for all factors that remain constant over a woman's childbearing years. We estimated the overall effects for birth spacing in a meta-analysis with random survey effects. We identified several factors known for their associations with neonatal, infant, and child mortality that are also associated with preceding birth interval. When estimating the effect of birth spacing on mortality, we found that regression adjustment for these factors does not substantially change the risk ratio for short birth intervals compared to an unadjusted mortality ratio. For birth intervals less than 18 months, standard

[Effects of a coaching program on comprehensive lifestyle modification for women with gestational diabetes mellitus].

PubMed

Ko, Jung Mi; Lee, Jong Kyung

2014-12-01

The purpose of this study was to investigate the effects of using a Coaching Program on Comprehensive Lifestyle Modification with pregnant women who have gestational diabetes. The research design for this study was a non-equivalent control group quasi-experimental study. Pregnant women with gestational diabetes were recruited from D women's hospital located in Gyeonggi Province from April to October, 2013. Participants in this study were 34 for the control group and 34 for the experimental group. The experimental group participated in the Coaching Program on Comprehensive Lifestyle Modification. The program consisted of education, small group coaching and telephone coaching over 4weeks. Statistical analysis was performed using the SPSS 21.0 program. There were significant improvements in self-care behavior, and decreases in depression, fasting blood sugar and HbA1C in the experimental group compared to the control group. However, no significant differences were found between the two groups for knowledge of gestational diabetes mellitus. The Coaching Program on Comprehensive Lifestyle Modification used in this study was found to be effective in improving self-care behavior and reducing depression, fasting blood sugar and HbA1C, and is recommended for use in clinical practice as an effective nursing intervention for pregnant women with gestational diabetes.

Factors confounding impedance catheter volume measurements in vitro.

PubMed

Bielefeld, M R; Cabreriza, S E; Spotnitz, H M

1993-06-01

The impedance catheter allows continuous measurement of ventricular volume. External influences have been described as causing parallel shifts in impedance-measured volumes; however, factors affecting impedance measurements in a nonparallel manner have not been fully characterized. Accordingly, an impedance catheter was placed inside a latex balloon into which known volumes of normal saline solution were injected. Conductive and nonconductive materials were individually placed within the balloon. Impedance was measured with materials touching (T) or not touching (NT) the catheter. Impedance-measured volumes were plotted versus actual volumes. Compared with the line of identity (LID), a statistical difference (p < 0.05) was found in the slopes in the presence of metallic objects only. These included a pacing lead (T, NT) (mT = 1.32m mNT = 1.29 versus mLID = 1.00), titanium (T) (mT = 1.68 versus mLID = 1.00), and aluminum (NT) (mNT = 0.72 versus mLID = 1.00). These changes in slope indicate nonparallel effects on impedance that confound the ability of the impedance catheter to determine volumes in vitro. These observations imply that serial calibration of both the slope constant (alpha) and the intercept (parallel conductance) of impedance may be necessary for in vivo measurements of ventricular volume based on impedance in the presence of metallic objects.

Effects of high hydrostatic pressure or hydrophobic modification on thermal stability of xanthine oxidase.

PubMed

Halalipour, Ali; Duff, Michael R; Howell, Elizabeth E; Reyes-De-Corcuera, José I

2017-08-01

The effect of high hydrostatic pressure (HHP) on the kinetics of thermal inactivation of xanthine oxidase (XOx) from bovine milk was studied. Inactivation of XOx followed pseudo-first-order kinetics at 0.1-300MPa and 55.0-70.0°C. High pressure up to at least 300MPa stabilized XOx at all the studied temperatures. The highest stabilization effect of HHP on XOx was at 200-300MPa at 55.0 and 58.6°C, and at 250-300MPa at 62.3-70.0°C. The stability of XOx increased 9.5 times at 300MPa and 70.0°C compared to atmospheric pressure at the same temperature. The activation energy of inactivation of XOx decreased with pressure and was 1.9 times less at 300MPa (97.0±8.2kJmol -1 ) than at 0.1MPa (181.7±12.1kJmol -1 ). High pressure decreased the dependence of the rate constant of inactivation to temperature effects compared to atmospheric pressure. The stabilizing effect of HHP on XOx was highest at 70.0°C where the activation volume of inactivation of XOx was 28.9±2.9cm 3 mol -1 . A second approach to try to increase XOx stability involved hydrophobic modification using aniline or benzoate. However, the thermal stability of XOx remained unaffected after 8-14 modifications of carboxyl side groups per XOx monomer with aniline, or 12-17 modifications of amino side groups per XOx monomer with benzoate. Copyright © 2017 Elsevier Inc. All rights reserved.

Confounding of the Association between Radiation Exposure from CT Scans and Risk of Leukemia and Brain Tumors by Cancer Susceptibility Syndromes.

PubMed

Meulepas, Johanna M; Ronckers, Cécile M; Merks, Johannes; Weijerman, Michel E; Lubin, Jay H; Hauptmann, Michael

2016-01-01

Recent studies linking radiation exposure from pediatric computed tomography (CT) to increased risks of leukemia and brain tumors lacked data to control for cancer susceptibility syndromes (CSS). These syndromes might be confounders because they are associated with an increased cancer risk and may increase the likelihood of CT scans performed in children. We identify CSS predisposing to leukemia and brain tumors through a systematic literature search and summarize prevalence and risk estimates. Because there is virtually no empirical evidence in published literature on patterns of CT use for most types of CSS, we estimate confounding bias of relative risks (RR) for categories of radiation exposure based on expert opinion about the current and previous patterns of CT scans among CSS patients. We estimate that radiation-related RRs for leukemia are not meaningfully confounded by Down syndrome, Noonan syndrome, or other CSS. In contrast, RRs for brain tumors may be overestimated due to confounding by tuberous sclerosis complex (TSC) while von Hippel-Lindau disease, neurofibromatosis type 1, or other CSS do not meaningfully confound. Empirical data on the use of CT scans among CSS patients are urgently needed. Our assessment indicates that associations with leukemia reported in previous studies are unlikely to be substantially confounded by unmeasured CSS, whereas brain tumor risks might have been overestimated due to confounding by TSC. Future studies should identify TSC patients in order to avoid overestimation of brain tumor risks due to radiation exposure from CT scans. ©2015 American Association for Cancer Research.

Effect of tooth profile modification on wear in internal gears

NASA Astrophysics Data System (ADS)

Tunalioglu, M. S.; Tuc, B.

2018-05-01

Internal gears are often used in the automotive industry when two gears are required to rotate in the same direction. Tooth shapes, slippage speeds at the beginning and end of meshing are different according to the external gears. Manufacturing of internal gears is more difficult than external gears. Thus, it is necessary to determine the working conditions and wear behavior of internal gears carefully. The profile modification method in terms of strength and surface tension of the gear mechanism are performed in order to increase the load-carrying capability. In this study, profile modification method was performed in the internal gears to reduce the wear on the teeth. For this purpose, the wear of the internal gears was theoretically investigated by adapting the Archard wear equation to the internal gears. Closed circuit power circulation system was designed and manufactured to experimentally investigate the wear in internal gears. With this system, wear tests of gears made of St 50 material without profile modification and different profile modifications were made and the results were compared. Experimental study was performed in the same loading and cycle time conditions to validate the theoretical results and it was seen that the results are compatible. According to the experimental results, it is seen that in the internal gears, when profile modification done the wear is decreased in the teeth tip region.

Silane surface modification effects on the electromagnetic properties of phosphatized iron-based SMCs

NASA Astrophysics Data System (ADS)

Fan, Liang-Fang; Hsiang, Hsing-I.; Hung, Jia-Jing

2018-03-01

It is difficult to achieve homogeneous phosphatized iron powder dispersion in organic resins during the preparation of soft magnetic composites (SMCs). Inhomogeneous iron powder mixing in organic resins generally leads to the formation of micro-structural defects in SMCs and hence causes the magnetic properties to become worse. Phosphatized iron powder dispersion in organic resins can be improved by coating the phosphatized iron powder surfaces with a coupling agent. This study investigated the (3-aminopropyl) triethoxysilane (APTES) surface modification effects on the electromagnetic properties of phosphatized iron-based soft magnetic composites (SMCs). The results showed that the phosphatized iron powder surface can be modified using APTES to improve the phosphatized iron powder and epoxy resin compatibility and hence enhance phosphate iron powder epoxy mixing. The tensile strength, initial permeability, rated current under DC-bias superposition and magnetic loss in SMCs prepared using phosphatized iron powders can be effectively improved using APTES surface modification, which provides a promising candidate for power chip inductor applications.

Carbon nanotubes toxicology and effects on metabolism and immunological modification in vitro and in vivo

NASA Astrophysics Data System (ADS)

Chiaretti, M.; Mazzanti, G.; Bosco, S.; Bellucci, S.; Cucina, A.; LeFoche, F.; Carru, G. A.; Mastrangelo, S.; Di Sotto, A.; Masciangelo, R.; Chiaretti, A. M.; Balasubramanian, C.; DeBellis, G.; Micciulla, F.; Porta, N.; Deriu, G.; Tiberia, A.

2008-11-01

The aim of this research is focused on the biological effects of multi wall carbon nanotubes (MWCNTs) on three different human cell types, laboratory animals in vivo, and immunological effects. Large numbers of researchers are directly involved in the handling of nanostructured materials such as MWCNTs and nanoparticles. It is important to assess the potential health risks related to their daily exposure to carbon nanotubes. The administration of sterilized nanosamples has been performed on laboratory animals, in both acute and chronic administration, and the pathological effects on the parenchymal tissues have been investigated. We studied the serum immunological modifications after intraperitoneal administration of the MWCNTs. We did not observe any antigenic reaction; the screening of ANA, anti-ENA, anti-cardiolipin, C-ANCA and P-ANCA was negative. No quantitative modification of immunoglobulins was observed, hence no modification of humoral immunity was documented. We also studied the effects of MWCNTs on the proliferation of three different cell types. MCF-7 showed a significant inhibition of proliferation for all conditions studied, whereas hSMCs demonstrated a reduction of cell growth only for the highest MWCNTs concentrations after 72 h. Also, no growth modification was observed in the Caco-2 cell line. We observed that a low quantity of MWCNTs does not provoke any inflammatory reaction. However, for future medical applications, it is important to realize prosthesis based on MWCNTs, through studying the corresponding implantation effects. Moreover, it has to be emphasized that this investigation does not address, at the moment, the carcinogenicity of MWCNTs, which requires a detailed follow-up investigation on the specific topic. In view of the subsequent and more extensive use of MWCNTs, especially in applications where carbon nanotubes are injected into the human body for drug delivery, as a contrast agent carrying entities for MRI, or as the basic

Ceramic modifications of porous titanium: effects on macrophage activation.

PubMed

Scislowska-Czarnecka, A; Menaszek, E; Szaraniec, B; Kolaczkowska, E

2012-12-01

Porous titanium is one of the most widely used implant materials because of its mechanical properties, however, it is also characterised by low bioactivity. To improve the above parameter we prepared three modifications of the porous (30 wt%) titanium (Ti) surface by covering it with bioactive hydroxyapatite (HA), bioglass (BG) and calcium silicate (CS). Subsequently we tested the impact of the modifications on macrophages directing the inflammatory response that might compromise the implant bioactivity. In the study we investigated the in vitro effects of the materials on murine cell line RAW 264.7 macrophage adherence, morphology and activation (production/release of metalloproteinase MMP-9 and pro- and anti-inflammatory cytokines). CS Ti decreased the macrophage adherence and up-regulated the release of several pro-inflammatory mediators, including TNF-α, IL-6, IL-12. Also HA Ti reduced the cell adherence but other parameters were generally not increased, except of TNF-α. In contrast, BG Ti improved macrophage adherence and either decreased production of multiple mediators (MMP-9, TNF-α, IFN-γ, MCP-1) or did not change it in comparison to the porous titanium. We can conclude that analyzing the effects on the inflammatory response initiated by macrophages in vitro, calcium silicate did not improve the biological properties of the porous titanium. The improved bioactivity of titanium was, however, achieved by the application of the hydroxyapatite and bioglass layers. The present in vitro results suggest that these materials, HA Ti and especially BG Ti, may be suitable for in vivo application and thus justify their further investigation. Copyright © 2012 Elsevier Ltd. All rights reserved.

An Improved Framework for Confound Regression and Filtering for Control of Motion Artifact in the Preprocessing of Resting-State Functional Connectivity Data

PubMed Central

Satterthwaite, Theodore D.; Elliott, Mark A.; Gerraty, Raphael T.; Ruparel, Kosha; Loughead, James; Calkins, Monica E.; Eickhoff, Simon B.; Hakonarson, Hakon; Gur, Ruben C.; Gur, Raquel E.; Wolf, Daniel H.

2013-01-01

Several recent reports in large, independent samples have demonstrated the influence of motion artifact on resting-state functional connectivity MRI (rsfc-MRI). Standard rsfc-MRI preprocessing typically includes regression of confounding signals and band-pass filtering. However, substantial heterogeneity exists in how these techniques are implemented across studies, and no prior study has examined the effect of differing approaches for the control of motion-induced artifacts. To better understand how in-scanner head motion affects rsfc-MRI data, we describe the spatial, temporal, and spectral characteristics of motion artifacts in a sample of 348 adolescents. Analyses utilize a novel approach for describing head motion on a voxelwise basis. Next, we systematically evaluate the efficacy of a range of confound regression and filtering techniques for the control of motion-induced artifacts. Results reveal that the effectiveness of preprocessing procedures on the control of motion is heterogeneous, and that improved preprocessing provides a substantial benefit beyond typical procedures. These results demonstrate that the effect of motion on rsfc-MRI can be substantially attenuated through improved preprocessing procedures, but not completely removed. PMID:22926292

The effects of linguistic modification on ESL students' comprehension of nursing course test items.

PubMed

Bosher, Susan; Bowles, Melissa

2008-01-01

Recent research has indicated that language may be a source of construct-irrelevant variance for non-native speakers of English, or English as a second language (ESL) students, when they take exams. As a result, exams may not accurately measure knowledge of nursing content. One accommodation often used to level the playing field for ESL students is linguistic modification, a process by which the reading load of test items is reduced while the content and integrity of the item are maintained. Research on the effects of linguistic modification has been conducted on examinees in the K-12 population, but is just beginning in other areas. This study describes the collaborative process by which items from a pathophysiology exam were linguistically modified and subsequently evaluated for comprehensibility by ESL students. Findings indicate that in a majority of cases, modification improved examinees' comprehension of test items. Implications for test item writing and future research are discussed.

Airfoil modification effects on subsonic and transonic pressure distributions and performance for the EA-6B airplane

NASA Technical Reports Server (NTRS)

Allison, Dennis O.; Sewall, William G.

1995-01-01

Longitudinal characteristics and wing-section pressure distributions are compared for the EA-6B airplane with and without airfoil modifications. The airfoil modifications were designed to increase low-speed maximum lift for maneuvering, while having a minimal effect on transonic performance. Section contour changes were confined to the leading-edge slat and trailing-edge flap regions of the wing. Experimental data are analyzed from tests in the Langley 16-Foot Transonic Tunnel on the baseline and two modified wing-fuselage configurations with the slats and flaps in their retracted positions. Wing modification effects on subsonic and transonic performance are seen in wing-section pressure distributions of the various configurations at similar lift coefficients. The modified-wing configurations produced maximum lift coefficients which exceeded those of the baseline configuration at low-speed Mach numbers (0.300 and 0.400). This benefit was related to the behavior of the wing upper surface leading-edge suction peak and the behavior of the trailing-edge pressure. At transonic Mach numbers (0.725 to 0.900), the wing modifications produced a somewhat stronger nose-down pitching moment, a slightly higher drag at low-lift levels, and a lower drag at higher lift levels.

Disability acquisition and mental health: effect modification by demographic and socioeconomic characteristics using data from an Australian longitudinal study.

PubMed

Aitken, Zoe; Simpson, Julie Anne; Bentley, Rebecca; Kavanagh, Anne Marie

2017-09-18

There is evidence of a causal relationship between disability acquisition and poor mental health, but the substantial heterogeneity in the magnitude of the effect is poorly understood and may be aetiologically informative. This study aimed to identify demographic and socioeconomic factors that modify the effect of disability acquisition on mental health. The Household, Income and Labour Dynamics in Australia Survey is a nationally representative longitudinal survey of Australian households that has been conducted annually since 2001. Four waves of data were included in this analysis, from 2011 to 2014. Individuals who acquired a disability (n=387) were compared with those who remained disability-free in all four waves (n=7936). Mental health was measured using the mental health subscale of the Short Form 36 (SF-36) general health questionnaire, which measures symptoms of depression, anxiety and psychological well-being. Linear regression models were fitted to estimate the effect of disability acquisition on mental health, testing for effect modification by key demographic and socioeconomic characteristics. To maximise causal inference, we used a propensity score approach with inverse probability of treatment weighting to control for confounding and multiple imputation using chained equations to assess the impact of missing data. On average, disability acquisition was associated with a 5-point decline in mental health score (estimated mean difference: -5.1, 95% CI -7.2 to -3.0). There was strong evidence that income and relationship status modified the effect, with more detrimental effects in the lowest (-12.5, 95% CI -18.5 to -6.5) compared with highest income quintile (-1.1, 95% CI -4.9 to 2.7) and for people not in a relationship (-8.8, 95% CI -12.9 to -4.8) compared with those who were (-3.7, 95% CI -6.1 to -1.4). Our results suggest that the detrimental effect of disability acquisition on mental health is substantially greater for socioeconomic

Are apparent negative effects of feeding GM MON810 maize to Atlantic salmon, Salmo salar, caused by confounding factors?

PubMed

Sissener, Nini H; Hemre, Gro-Ingunn; Lall, Santosh P; Sagstad, Anita; Petersen, Kjell; Williams, Jason; Rohloff, Jens; Sanden, Monica

2011-07-01

The present study was conducted to follow up on apparent differences in growth, relative organ sizes, cellular stress and immune function in Atlantic salmon fed feed containing GM Bacillus thuringiensis maize compared with feed containing the non-modified parental maize line. Gene expression profiling on the distal intestinal segment and liver was performed by microarray, and selected genes were followed up by quantitative PCR (qPCR). In the liver, qPCR revealed some differentially regulated genes, including up-regulation of gelsolin precursor, down-regulation of ferritin heavy subunit and a tendency towards down-regulation of metallothionein (MT)-B. This, combined with the up-regulation of anti-apoptotic protein NR13 and similar tendencies for ferritin heavy chain and MT-A and -B in the distal intestine, suggests changes in cellular stress/antioxidant status. This corresponds well with and strengthens previous findings in these fish. To exclude possible confounding factors, the maize ingredients were analysed for mycotoxins and metabolites. The GM maize contained 90 μg/kg of deoxynivalenol (DON), while the non-GM maize was below the detection limit. Differences were also observed in the metabolite profiles of the two maize varieties, some of which seemed connected to the mycotoxin level. The effects on salmon observed in the present and previous studies correspond relatively well with the effects of DON as reported in the literature for other production animals, but knowledge regarding effects and harmful dose levels in fish is scarce. Thus, it is difficult to conclude whether the observed effects are caused by the DON level or by some other aspect of the GM maize ingredient.

Crash Modification Factors for Chevrons in Iowa

DOT National Transportation Integrated Search

2018-02-02

Although chevron alignment signs have been utilized for some time along horizontal curves, their effectiveness is not well documented. The Crash Modification Factors Clearinghouse includes crash modification factors (CMFs) for chevrons from 0.41 to 1...

The effects of size and surface modification of amorphous silica particles on biodistribution and liver metabolism in mice

NASA Astrophysics Data System (ADS)

Lu, Xiaoyan; Ji, Cai; Jin, Tingting; Fan, Xiaohui

2015-05-01

Engineered nanoparticles, with unconventional properties, are promising platforms for biomedical applications. Since they may interact with a wide variety of biomolecules, it is critical to understand the impact of the physicochemical properties of engineered nanoparticles on biological systems. In this study, the effects of particle size and surface modification alone or in combination of amorphous silica particles (SPs) on biological responses were determined using a suite of general toxicological assessments and metabonomics analysis in mice model. Our results suggested that amino or carboxyl surface modification mitigated the liver toxicity of plain-surface SPs. 30 nm SPs with amino surface modification were found to be the most toxic SPs among all the surface-modified SP treatments at the same dosage. When treatment dose was increased, submicro-sized SPs with amino or carboxyl surface modification also induced liver toxicity. Biodistribution studies suggested that 70 nm SPs were mainly accumulated in liver and spleen regardless of surface modifications. Interestingly, these two organs exhibited different uptake trends. Furthermore, metabonomics studies indicated that surface modification plays a more dominant role to affect the liver metabolism than particle size.

Enhancing the estimation of blood pressure using pulse arrival time and two confounding factors.

PubMed

Baek, Hyun Jae; Kim, Ko Keun; Kim, Jung Soo; Lee, Boreom; Park, Kwang Suk

2010-02-01

A new method of blood pressure (BP) estimation using multiple regression with pulse arrival time (PAT) and two confounding factors was evaluated in clinical and unconstrained monitoring situations. For the first analysis with clinical data, electrocardiogram (ECG), photoplethysmogram (PPG) and invasive BP signals were obtained by a conventional patient monitoring device during surgery. In the second analysis, ECG, PPG and non-invasive BP were measured using systems developed to obtain data under conditions in which the subject was not constrained. To enhance the performance of BP estimation methods, heart rate (HR) and arterial stiffness were considered as confounding factors in regression analysis. The PAT and HR were easily extracted from ECG and PPG signals. For arterial stiffness, the duration from the maximum derivative point to the maximum of the dicrotic notch in the PPG signal, a parameter called TDB, was employed. In two experiments that normally cause BP variation, the correlation between measured BP and the estimated BP was investigated. Multiple-regression analysis with the two confounding factors improved correlation coefficients for diastolic blood pressure and systolic blood pressure to acceptable confidence levels, compared to existing methods that consider PAT only. In addition, reproducibility for the proposed method was determined using constructed test sets. Our results demonstrate that non-invasive, non-intrusive BP estimation can be obtained using methods that can be applied in both clinical and daily healthcare situations.

Quantification of Treatment Effect Modification on Both an Additive and Multiplicative Scale

PubMed Central

Girerd, Nicolas; Rabilloud, Muriel; Pibarot, Philippe; Mathieu, Patrick; Roy, Pascal

2016-01-01

Background In both observational and randomized studies, associations with overall survival are by and large assessed on a multiplicative scale using the Cox model. However, clinicians and clinical researchers have an ardent interest in assessing absolute benefit associated with treatments. In older patients, some studies have reported lower relative treatment effect, which might translate into similar or even greater absolute treatment effect given their high baseline hazard for clinical events. Methods The effect of treatment and the effect modification of treatment were respectively assessed using a multiplicative and an additive hazard model in an analysis adjusted for propensity score in the context of coronary surgery. Results The multiplicative model yielded a lower relative hazard reduction with bilateral internal thoracic artery grafting in older patients (Hazard ratio for interaction/year = 1.03, 95%CI: 1.00 to 1.06, p = 0.05) whereas the additive model reported a similar absolute hazard reduction with increasing age (Delta for interaction/year = 0.10, 95%CI: -0.27 to 0.46, p = 0.61). The number needed to treat derived from the propensity score-adjusted multiplicative model was remarkably similar at the end of the follow-up in patients aged < = 60 and in patients >70. Conclusions The present example demonstrates that a lower treatment effect in older patients on a relative scale can conversely translate into a similar treatment effect on an additive scale due to large baseline hazard differences. Importantly, absolute risk reduction, either crude or adjusted, can be calculated from multiplicative survival models. We advocate for a wider use of the absolute scale, especially using additive hazard models, to assess treatment effect and treatment effect modification. PMID:27045168

The impact of cold spells on mortality and effect modification by cold spell characteristics

NASA Astrophysics Data System (ADS)

Wang, Lijun; Liu, Tao; Hu, Mengjue; Zeng, Weilin; Zhang, Yonghui; Rutherford, Shannon; Lin, Hualiang; Xiao, Jianpeng; Yin, Peng; Liu, Jiangmei; Chu, Cordia; Tong, Shilu; Ma, Wenjun; Zhou, Maigeng

2016-12-01

In China, the health impact of cold weather has received little attention, which limits our understanding of the health impacts of climate change. We collected daily mortality and meteorological data in 66 communities across China from 2006 to 2011. Within each community, we estimated the effect of cold spell exposure on mortality using a Distributed Lag Nonlinear Model (DLNM). We also examined the modification effect of cold spell characteristics (intensity, duration, and timing) and individual-specific factors (causes of death, age, gender and education). Meta-analysis method was finally used to estimate the overall effects. The overall cumulative excess risk (CER) of non-accidental mortality during cold spell days was 28.2% (95% CI: 21.4%, 35.3%) compared with non-cold spell days. There was a significant increase in mortality when the cold spell duration and intensity increased or occurred earlier in the season. Cold spell effects and effect modification by cold spell characteristics were more pronounced in south China. The elderly, people with low education level and those with respiratory diseases were generally more vulnerable to cold spells. Cold spells statistically significantly increase mortality risk in China, with greater effects in southern China. This effect is modified by cold spell characteristics and individual-level factors.

Overview of potential procedural and participant-related confounds for neuroimaging of the resting state

PubMed Central

Duncan, Niall W.; Northoff, Georg

2013-01-01

Studies of intrinsic brain activity in the resting state have become increasingly common. A productive discussion of what analysis methods are appropriate, of the importance of physiologic correction and of the potential interpretations of results has been ongoing. However, less attention has been paid to factors other than physiologic noise that may confound resting-state experiments. These range from straightforward factors, such as ensuring that participants are all instructed in the same manner, to more obscure participant-related factors, such as body weight. We provide an overview of such potentially confounding factors, along with some suggested approaches for minimizing their impact. A particular theme that emerges from the overview is the range of systematic differences between types of study groups (e.g., between patients and controls) that may influence resting-state study results. PMID:22964258

Confounding of the association between radiation exposure from CT scans and risk of leukemia and brain tumors by cancer susceptibility syndromes.

PubMed

Meulepas, Johanna M; Ronckers, Cécile M; Merks, Johannes; Weijerman, Michel E; Lubin, Jay H; Hauptmann, Michael

2016-12-01

Recent studies linking radiation exposure from pediatric computed tomography (CT) to increased risks of leukemia and brain tumors lacked data to control for cancer susceptibility syndromes (CSS). These syndromes might be confounders because they are associated with an increased cancer risk and may increase the likelihood of pediatric CT scans. We identify CSS predisposing to leukemia and brain tumors through a systematic literature search and summarize prevalence and risk. Since empirical evidence is lacking in published literature on patterns of CT use for most types of CSS, we estimate confounding bias of relative risks (RR) for categories of radiation exposure based on expert opinion about patterns of CT scans among CSS patients. We estimate that radiation-related RRs for leukemia are not meaningfully confounded by Down syndrome, Noonan syndrome and other CSS. Moreover, tuberous sclerosis complex, von Hippel-Lindau disease, neurofibromatosis type 1 and other CSS do not meaningfully confound RRs for brain tumors. Empirical data on the use of CT scans among CSS patients is urgently needed. Our assessment indicates that associations with radiation exposure from pediatric CT scans and leukemia or brain tumors reported in previous studies are unlikely to be substantially confounded by unmeasured CSS.

Duration perception of emotional stimuli: Using evaluative conditioning to avoid sensory confounds.

PubMed

Kliegl, Katrin M; Watrin, Luc; Huckauf, Anke

2015-01-01

It has been found that emotional pictures are estimated to last longer than neutral ones. However, emotional and neutral stimuli often differ in their physical characteristics, too. Since this might also affect time perception, we present a method disentangling a possible confounding regarding the processing of physically different stimulus material. In the evaluative condition paradigm, participants, at first, learnt the association of neutral images with a certain Landolt ring and of emotional images with another Landolt ring with a different gap position. The conditioned Landolt rings were subsequently used in a temporal bisection task. In two experiments, the results revealed a temporal overestimation of Landolt rings conditioned with emotional pictures compared to neutral pictures showing that the temporal overestimation of emotional stimuli cannot be attributed to perceptual differences between neutral and emotional stimuli. The method provides the potential for investigating emotional effects on various perceptual processes.

The Effects of Equipment Modification on Children's Self-Efficacy and Basketball Shooting Performance.

ERIC Educational Resources Information Center

Chase, Melissa A.; And Others

1994-01-01

Reports a study that examined the effects of modification of basketball size and basket height on shooting performance and self-efficacy of children ages 9-12 years. Subjects completed a self-efficacy questionnaire before and after shooting 10 baskets under 4 conditions. Self-efficacy was highest when children shot at a lower basket. (SM)

Assessing Mediation Using Marginal Structural Models in the Presence of Confounding and Moderation

ERIC Educational Resources Information Center

Coffman, Donna L.; Zhong, Wei

2012-01-01

This article presents marginal structural models with inverse propensity weighting (IPW) for assessing mediation. Generally, individuals are not randomly assigned to levels of the mediator. Therefore, confounders of the mediator and outcome may exist that limit causal inferences, a goal of mediation analysis. Either regression adjustment or IPW…

Short-term effects of air temperature on mortality and effect modification by air pollution in three cities of Bavaria, Germany: a time-series analysis.

PubMed

Breitner, Susanne; Wolf, Kathrin; Devlin, Robert B; Diaz-Sanchez, David; Peters, Annette; Schneider, Alexandra

2014-07-01

Air temperature has been shown to be associated with mortality; however, only very few studies have been conducted in Germany. This study examined the association between daily air temperature and cause-specific mortality in Bavaria, Southern Germany. Moreover, we investigated effect modification by age and ambient air pollution. We obtained data from Munich, Nuremberg as well as Augsburg, Germany, for the period 1990 to 2006. Data included daily cause-specific death counts, mean daily meteorology and air pollution concentrations (particulate matter with a diameter<10 μm [PM10] and maximum 8-h ozone). We used Poisson regression models combined with distributed lag non-linear models adjusting for long-term trend, calendar effects, and meteorological factors. Air pollutant concentrations were categorized into three levels, and an interaction term was included to quantify potential effect modification of the air temperature effects. The temperature-mortality relationships were non-linear for all cause-specific mortality categories showing U- or J-shaped curves. An increase from the 90th (20.0 °C) to the 99th percentile (24.8 °C) of 2-day average temperature led to an increase in non-accidental mortality by 11.4% (95% CI: 7.6%-15.3%), whereas a decrease from the 10th (-1.0 °C) to the 1st percentile (-7.5 °C) in the 15-day average temperature resulted in an increase of 6.2% (95% CI: 1.8%-10.8%). The very old were found to be most susceptible to heat effects. Results also suggested some effect modification by ozone, but not for PM10. Results indicate that both very low and very high air temperature increase cause-specific mortality in Bavaria. Results also pointed to the importance of considering effect modification by age and ozone in assessing temperature effects on mortality. Copyright © 2014 Elsevier B.V. All rights reserved.

The effect of lifestyle modification on physical fitness and work ability in different workstyles.

PubMed

Ohta, Masanori; Okufuji, Tatsuya; Matsushima, Yasuyuki; Ikeda, Masaharu

2004-12-01

It is generally considered that physical fitness is affected by daily life activities including leisure time activity and working time activity. The aim of this study is to investigate the effects of different levels of physical activity at work on physical fitness, analyze the effects of 12-week lifestyle modification outside of working hours on physical fitness, work satisfaction and subjective symptoms, and to consider the role of lifestyle modification in occupational health. Lifestyle modification, consisting of aerobic exercise and diet counseling, was conducted for 12 weeks. The data before and after the intervention from 49 male workers were obtained. Physical fitness such as exercise endurance, flexibility, agility, balance, muscular strength, muscular endurance, and muscular power was measured before and after the intervention. The subjects were asked to fill out questionnaires about their work activities, subjective complaints, and work satisfaction. Subjects were divided into active work group (n = 14) and sedentary work group (n = 35) for analysis according to their work activities. As for differences in physical fitness due to different levels of physical activity, the active work group had superior exercise endurance and balance compared to the sedentary work group. In addition, the sedentary work group tended to experience greater fatigue than the active work group. In the active work group, flexibility and muscular strength were significantly increased with lifestyle modification and, in the sedentary work group, exercise endurance, flexibility and muscular endurance were significantly improved while balance also showed a tendency to improve. In the sedentary work group, lifestyle modification resulted in reduced fatigue and stiff neck as well as an increased work satisfaction. In the active work group, no change was observed in complaints or work satisfaction, but improved physical fitness led to a reduction in subjective complaints and an

Effect of diuretics on fetal growth: A drug effect or confounding by indication? Pooled Danish and Scottish cohort data

PubMed Central

Olesen, Charlotte; de Vries, Corinne S; Thrane, Nana; MacDonald, Tom M; Larsen, Helle; Sørensen, Henrik Toft

2001-01-01

Aims The diabetogenic effect of diuretics, as well as the indication for prescribing them, may impact on fetal growth. We analysed whether the purchase of prescription drugs for diuretics during pregnancy was associated with measures of fetal growth. Methods During 1991–98 all women who purchased prescription drugs for diuretics during pregnancy were identified in the Northern Jutland Prescription Database (NJDP), Denmark, and in the Medicines Monitoring Unit's Database (MEMO), Scotland. Information on birth weight and gestational age was obtained from the Danish Birth Registry, the Danish Hospital Discharge Registry and the Scottish Tayside Neonatal Database. Information on diabetes, hypertension and prepregnancy weight were obtained by hospital record review in a sample of women in the Danish cohort. Women who did not purchase prescription diuretics during pregnancy were used as a reference group in both cohorts. Results Danish women who purchased prescription loop diuretics during pregnancy gave birth to infants with higher birth weights than women who did not use diuretics; mean difference 104.7 g (95% CI; 2.6, 206.9). However, the high prevalence of diabetes (10.3%) among Danish women who purchased prescription loop diuretics during pregnancy might explain this result. Both the Danish and the Scottish women who purchased prescription diuretics during their pregnancy were at increased risk of preterm delivery (< 37 completed weeks); ORs: 1.8 (CI; 1.2, 2.7)NJDP, 1.9 (CI; 0.9, 4.3)MEMO. The proportion of hypertension among women who purchased prescription thiazides was 15.8%, and the risk of having an infant with a birth weight (BW) < 2500 g was increased; ORs: 2.6 (CI; 1.4, 5.0)NJDP, 2.4 (CI; 0.8, 7.8)MEMO. Conclusions Prescribing diuretics during pregnancy was associated with differences in birth weight and incidence of preterm delivery. Confounding by indication may explain the findings. PMID:11259987

Effect of thermal modification on rheological properties of polyethylene blends

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siriprumpoonthum, Monchai; Nobukawa, Shogo; Yamaguchi, Masayuki, E-mail: m-yama@jaist.ac.jp

2014-03-15

We examined the effects of thermal modification under flow field on the rheological properties of linear low-density polyethylene (LLDPE) with high molecular weight, low-density polyethylene (LDPE), and their blends, without thermal stabilizer. Although structural changes during processing are not detected by size extrusion chromatography or nuclear magnetic resonance spectroscopy, linear viscoelastic properties changed greatly, especially for the LLDPE. A cross-linking reaction took place, leading to, presumably, star-shaped long-chain branches. Consequently, the modified LLDPE, having high zero-shear viscosity, became a thermorheologically complex melt. Moreover, it should be noted that the drawdown force, defined as the uniaxial elongational force at a constantmore » draw ratio, was significantly enhanced for the blends. Enhancement of elongational viscosity was also detected. The drawdown force and elongational viscosity are marked for the thermally modified blend as compared with those for the blend of thermally modified pure components. Intermolecular cross-linking reactions between LDPE and LLDPE, yielding polymers with more than two branch points per chain, result in marked strain-hardening in the elongational viscosity behavior even at small strain. The recovery curve of the oscillatory modulus after the shear modification is further evidence of a branched structure.« less

Optimal Control Modification for Time-Scale Separated Systems

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T.

2012-01-01

Recently a new optimal control modification has been introduced that can achieve robust adaptation with a large adaptive gain without incurring high-frequency oscillations as with the standard model-reference adaptive control. This modification is based on an optimal control formulation to minimize the L2 norm of the tracking error. The optimal control modification adaptive law results in a stable adaptation in the presence of a large adaptive gain. This study examines the optimal control modification adaptive law in the context of a system with a time scale separation resulting from a fast plant with a slow actuator. A singular perturbation analysis is performed to derive a modification to the adaptive law by transforming the original system into a reduced-order system in slow time. A model matching conditions in the transformed time coordinate results in an increase in the actuator command that effectively compensate for the slow actuator dynamics. Simulations demonstrate effectiveness of the method.

Meta-analysis of lung cancer in asphalt roofing and paving workers with external adjustment for confounding by coal tar

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fayerweather, W.E.

2007-07-01

The study's objectives were to update Partanen's and Boffetta's 1994 meta-analysis of lung cancer among roofing and paving asphalt workers and explore the role of coal tar in explaining the statistical heterogeneity among these studies. Information retrieval strategies and eligibility criteria were defined for identifying the epidemiologic studies to be included in the analysis. The relative risk ratio (RR) for lung cancer was selected as the effect measure of interest. Coal tar bias factors were developed and used to externally adjust each eligible study's published RR for confounding by coal tar. The meta-Relative Risk (meta-RR) and its variance were estimatedmore » by general variance-based methods. Heterogeneity of the RRs was assessed by heterogeneity chi-square and I{sup 2} tests. The results from this update were similar to those in Partanen's and Boffetta's original meta-analysis. Although the meta-RRs for the roofers and the pavers were no longer statistically significantly different from one another, significant heterogeneity remained within each of the coal tar-adjusted sectors. Meta-analysis of non-experimental epidemiologic studies is subject to significant uncertainties as is externally correcting studies for confounding. Given these uncertainties, the specific quantitative estimates in this (or any similar) analysis must be viewed with caution. Nevertheless, this analysis provides support for the hypothesis proposed by several major reviewers that confounding by coal tar-related PAH exposures may explain most or all of the lung cancer risks found in the epidemiologic literature on asphalt roofing and paving workers.« less

Eliminating the blood-flow confounding effect in intravoxel incoherent motion (IVIM) using the non-negative least square analysis in liver.

PubMed

Gambarota, Giulio; Hitti, Eric; Leporq, Benjamin; Saint-Jalmes, Hervé; Beuf, Olivier

2017-01-01

Tissue perfusion measurements using intravoxel incoherent motion (IVIM) diffusion-MRI are of interest for investigations of liver pathologies. A confounding factor in the perfusion quantification is the partial volume between liver tissue and large blood vessels. The aim of this study was to assess and correct for this partial volume effect in the estimation of the perfusion fraction. MRI experiments were performed at 3 Tesla with a diffusion-MRI sequence at 12 b-values. Diffusion signal decays in liver were analyzed using the non-negative least square (NNLS) method and the biexponential fitting approach. In some voxels, the NNLS analysis yielded a very fast-decaying component that was assigned to partial volume with the blood flowing in large vessels. Partial volume correction was performed by biexponential curve fitting, where the first data point (b = 0 s/mm 2 ) was eliminated in voxels with a very fast-decaying component. Biexponential fitting with partial volume correction yielded parametric maps with perfusion fraction values smaller than biexponential fitting without partial volume correction. The results of the current study indicate that the NNLS analysis in combination with biexponential curve fitting allows to correct for partial volume effects originating from blood flow in IVIM perfusion fraction measurements. Magn Reson Med 77:310-317, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

78 FR 20137 - Probable Economic Effect of Certain Modifications to the North American Free Trade Agreement...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-03

... INTERNATIONAL TRADE COMMISSION [Investigation No. TA-103-027] Probable Economic Effect of Certain... investigation No. TA-103-027, Probable Economic Effect of Certain Modifications to the North American Free Trade... reached agreement in principle with representatives of the governments of Canada and Mexico on proposed...

Meta-Analysis of the Effects of Academic Interventions and Modifications on Student Behavior Outcomes

ERIC Educational Resources Information Center

Warmbold-Brann, Kristy; Burns, Matthew K.; Preast, June L.; Taylor, Crystal N.; Aguilar, Lisa N.

2017-01-01

The current study examined the effect of academic interventions and modifications on behavioral outcomes in a meta-analysis of 32 single-case design studies. Academic interventions included modifying task difficulty, providing instruction in reading, mathematics, or writing, and contingent reinforcement for academic performance. There was an…

Soil acidification as a confounding factor on metal phytotoxicity in soils spiked with copper-rich mine wastes.

PubMed

Ginocchio, Rosanna; De la Fuente, Luz María; Sánchez, Pablo; Bustamante, Elena; Silva, Yasna; Urrestarazu, Paola; Rodríguez, Patricio H

2009-10-01

Pollution of soil with mine wastes results in both Cu enrichment and soil acidification. This confounding effect may be very important in terms of phytotoxicity, because pH is a key parameter influencing Cu solubility in soil solution. Laboratory toxicity tests were used to assess the effect of acidification by acidic mine wastes on Cu solubility and on root elongation of barley (Hordeum vulgare L.). Three contrasting substrates (two soils and a commercial sand) and two acidic, Cu-rich mine wastes (oxidized tailings [OxT] and smelter dust [SmD]) were selected as experimental materials. Substrates were spiked with a fixed amount of either SmD or OxT, and the pH of experimental mixtures was then modified in the range of 4.0 to 6.0 and 7.0 using PIPES (piperazine-1,4-bis(2-ethanesulfonic acid)), MES (2-(N-morpholino)ethanesulfonic acid), and MOPS (3-(N-Morpholino)-propanesulfonic acid) buffers. Chemical (pore-water Cu and pH) and toxicological (root length of barley plants) parameters were determined for experimental mixtures. Addition of SmD and OxT to substrates resulted in acidification (0.11-1.16 pH units) and high levels of soluble Cu and Zn. Neutralization of experimental mixtures with MES (pH 6.0) and MOPS (pH 7.0) buffers resulted in a marked decrease in soluble Cu and Zn, but the intensity of the effect was substrate-dependent. Adjustment of soil pH above the range normally considered to be toxic to plants (pH in water extract, > 5.5) significantly reduced metal toxicity in barley, but phytotoxicity was not completely eliminated. The present results stress the importance of considering confounding effects on derivation of toxicity thresholds to plants when using laboratory phytotoxicity tests.

Neuroticism explains unwanted variance in Implicit Association Tests of personality: possible evidence for an affective valence confound.

PubMed

Fleischhauer, Monika; Enge, Sören; Miller, Robert; Strobel, Alexander; Strobel, Anja

2013-01-01

Meta-analytic data highlight the value of the Implicit Association Test (IAT) as an indirect measure of personality. Based on evidence suggesting that confounding factors such as cognitive abilities contribute to the IAT effect, this study provides a first investigation of whether basic personality traits explain unwanted variance in the IAT. In a gender-balanced sample of 204 volunteers, the Big-Five dimensions were assessed via self-report, peer-report, and IAT. By means of structural equation modeling (SEM), latent Big-Five personality factors (based on self- and peer-report) were estimated and their predictive value for unwanted variance in the IAT was examined. In a first analysis, unwanted variance was defined in the sense of method-specific variance which may result from differences in task demands between the two IAT block conditions and which can be mirrored by the absolute size of the IAT effects. In a second analysis, unwanted variance was examined in a broader sense defined as those systematic variance components in the raw IAT scores that are not explained by the latent implicit personality factors. In contrast to the absolute IAT scores, this also considers biases associated with the direction of IAT effects (i.e., whether they are positive or negative in sign), biases that might result, for example, from the IAT's stimulus or category features. None of the explicit Big-Five factors was predictive for method-specific variance in the IATs (first analysis). However, when considering unwanted variance that goes beyond pure method-specific variance (second analysis), a substantial effect of neuroticism occurred that may have been driven by the affective valence of IAT attribute categories and the facilitated processing of negative stimuli, typically associated with neuroticism. The findings thus point to the necessity of using attribute category labels and stimuli of similar affective valence in personality IATs to avoid confounding due to recoding.

Modifications of Glycans: Biological Significance and Therapeutic Opportunities

PubMed Central

Muthana, Saddam M.; Campbell, Christopher; Gildersleeve, Jeffrey C.

2012-01-01

Carbohydrates play a central role in a wide range of biological processes. As with nucleic acids and proteins, modifications of specific sites within the glycan chain can modulate a carbohydrate’s overall biological function. For example, acylation, methylation, sulfation, epimerization, and phosphorylation can occur at various positions within a carbohydrate to modulate bioactivity. Therefore, there is significant interest in identifying discrete carbohydrate modifications and understanding their biological effects. Additionally, enzymes that catalyze those modifications and proteins that bind modified glycans provide numerous targets for therapeutic intervention. This review will focus on modifications of glycans that occur after the oligomer/polymer has been assembled, generally referred to as postglycosylational modifications. PMID:22195988

Influence of GSTM1 and GSTT1 genotypes and confounding factors on the frequency of sister chromatid exchange and micronucleus among road construction workers.

PubMed

Kumar, Anil; Yadav, Anita; Giri, Shiv Kumar; Dev, Kapil; Gautam, Sanjeev Kumar; Gupta, Ranjan; Aggarwal, Neeraj

2011-07-01

In the present study, we have investigated the influence of polymorphism of GSTM1 and GSTT1 genes and confounding factors such as age, sex, exposure duration and consumption habits on cytogenetic biomarkers. Frequency of sister chromatid exchanges (SCEs), high frequency cell (HFC) and cytokinesis blocked micronuclei (CBMN) were evaluated in peripheral blood lymphocytes of 115 occupationally exposed road construction workers and 105 unexposed individuals. The distribution of null and positive genotypes of glutathione-S transferase gene was evaluated by multiplex PCR among control and exposed subjects. An increased frequency of CBMN (7.03±2.08); SCE (6.95±1.76) and HFC (6.28±1.69) were found in exposed subjects when compared to referent (CBMN - 3.35±1.10; SCE - 4.13±1.30 and HFC - 3.98±1.56). These results were found statistically significant at p<0.05. When the effect of confounding factors on the frequency of studied biomarkers was evaluated, a strong positive interaction was found. The individuals having GSTM1 and GSTT1 null genotypes had higher frequency of CBMN, SCE and HFC. The association between GSTM1 and GSTT1 genotypes and studied biomarkers was found statistically significant at p<0.05. Our findings suggest that individuals having null type of GST are more susceptible to cytogenetic damage by occupational exposure regardless of confounding factors. There is a significant effect of polymorphism of these genes on cytogenetic biomarkers which are considered as early effects of genotoxic carcinogens. Copyright © 2011 Elsevier Ltd. All rights reserved.

Oxidative stress in drug-naïve first episode patients with schizophrenia and major depression: effects of disease acuity and potential confounders.

PubMed

Jordan, Wolfgang; Dobrowolny, Henrik; Bahn, Sabine; Bernstein, Hans-Gert; Brigadski, Tanja; Frodl, Thomas; Isermann, Berend; Lessmann, Volkmar; Pilz, Jürgen; Rodenbeck, Andrea; Schiltz, Kolja; Schwedhelm, Edzard; Tumani, Hayrettin; Wiltfang, Jens; Guest, Paul C; Steiner, Johann

2018-03-01

Oxidative stress and immune dysregulation have been linked to schizophrenia and depression. However, it is unknown whether these factors are related to the pathophysiology or whether they are an epiphenomenon. Inconsistent oxidative stress-related findings in previous studies may have resulted from the use of different biomarkers which show disparate aspects of oxidative stress. Additionally, disease severity, medication, smoking, endocrine stress axis activation and obesity are potential confounders. In order to address some of these shortcomings, we have analyzed a broader set of oxidative stress biomarkers in our exploratory study, including urinary 8-iso-prostaglandin F2α (8-iso-PGF2α), 8-OH-2-deoyxguanosine (8-OH-2-dG), and blood levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione S-transferase (GST) in acutely ill drug-naïve first episode patients with schizophrenia (n = 22), major depression (n = 18), and controls (n = 43). Possible confounding factors were considered, and patients were followed-up after 6 weeks of treatment. No differences were observed regarding 8-OH-2-dG, MDA and GST. At baseline, 8-iso-PGF2α levels were higher in patients with schizophrenia (p = 0.004) and major depression (p = 0.037), with a trend toward higher SOD concentrations in schizophrenia (p = 0.053). After treatment, schizophrenia patients showed a further increase in 8-iso-PGF2α (p = 0.016). These results were not related to age, sex, disease severity, medication or adipose tissue mass. However, 8-iso-PGF2α was associated with smoking, endocrine stress axis activation, C-reactive protein levels and low plasma concentrations of brain-derived neurotrophic factor. This study suggests a role of lipid peroxidation particularly in drug-naïve acutely ill schizophrenia patients and highlights the importance of taking into account other confounding factors in biomarker studies.

Accuracy and the Effect of Possible Subject-Based Confounders of Magnitude-Based MRI for Estimating Hepatic Proton Density Fat Fraction in Adults, Using MR Spectroscopy as Reference

PubMed Central

Heba, Elhamy R.; Desai, Ajinkya; Zand, Kevin A.; Hamilton, Gavin; Wolfson, Tanya; Schlein, Alexandra N.; Gamst, Anthony; Loomba, Rohit; Sirlin, Claude B.; Middleton, Michael S.

2016-01-01

Purpose To determine the accuracy and the effect of possible subject-based confounders of magnitude-based magnetic resonance imaging (MRI) for estimating hepatic proton density fat fraction (PDFF) for different numbers of echoes in adults with known or suspected nonalcoholic fatty liver disease, using MR spectroscopy (MRS) as a reference. Materials and Methods In this retrospective analysis of 506 adults, hepatic PDFF was estimated by unenhanced 3.0T MRI, using right-lobe MRS as reference. Regions of interest placed on source images and on six-echo parametric PDFF maps were colocalized to MRS voxel location. Accuracy using different numbers of echoes was assessed by regression and Bland–Altman analysis; slope, intercept, average bias, and R2 were calculated. The effect of age, sex, and body mass index (BMI) on hepatic PDFF accuracy was investigated using multivariate linear regression analyses. Results MRI closely agreed with MRS for all tested methods. For three- to six-echo methods, slope, regression intercept, average bias, and R2 were 1.01–0.99, 0.11–0.62%, 0.24–0.56%, and 0.981–0.982, respectively. Slope was closest to unity for the five-echo method. The two-echo method was least accurate, underestimating PDFF by an average of 2.93%, compared to an average of 0.23–0.69% for the other methods. Statistically significant but clinically nonmeaningful effects on PDFF error were found for subject BMI (P range: 0.0016 to 0.0783), male sex (P range: 0.015 to 0.037), and no statistically significant effect was found for subject age (P range: 0.18–0.24). Conclusion Hepatic magnitude-based MRI PDFF estimates using three, four, five, and six echoes, and six-echo parametric maps are accurate compared to reference MRS values, and that accuracy is not meaningfully confounded by age, sex, or BMI. PMID:26201284

Impacts of temperature change on ambulance dispatches and seasonal effect modification.

PubMed

Cheng, Jian; Xu, Zhiwei; Zhao, Desheng; Xie, Mingyu; Yang, Huihui; Wen, Liying; Li, Kesheng; Su, Hong

2016-12-01

Ambulance dispatch is a proxy of acute health outcomes, and growing epidemiological evidence documented its relation to extreme temperature events. Research, however, on short-term temperature change and ambulance dispatches is scarce. We aimed to investigate the effect of short-term temperature change on ambulance dispatches and potential modification by season. Daily data on ambulance dispatch and weather factors were collected in Huainan, a Chinese inland city from December 2011 through December 2013. A Poison generalized linear regression model combined with distributed lag nonlinear model was constructed to examine the association of temperature change between neighboring days (TCN) with ambulance dispatches. The effect modification by season was also examined. There were 48,700 ambulance attendances during the study period. A statistically significant association of TCN with ambulance dispatches was observed. Temperature rise between neighboring days (TCN > 0) was associated with elevated adverse risk of ambulance dispatches, and the effects appeared to be acute (lag0, on the current day) and could last for at least a week, while temperature drop between neighboring days (TCN < 0) had a protective effect. For a 1 °C increase of TCN at lag0 and lag06 (on the 7-day moving average), the risk of ambulance dispatches increased by 2 % (95 % CI 1-3 %) and 7 (95 % CI 1-13 %), respectively. Extreme TCN increase (95th percentile, 3.3 °C vs. 0 °C) at lag0 and lag05 was accompanied by 6 (95 % CI 3-8 %) and 27 % (95 % CI 12-44 %) increase in ambulance dispatches. Ambulance dispatches were more vulnerable to extremely great temperature rise in summer and autumn. TCN was adopted for the first time to quantify the impact of short-term temperature change on ambulance dispatches. Temperature drop between neighboring days (TCN < 0) had a protective effect on ambulance dispatches, while temperature rise between neighboring days (TCN > 0) could acutely

The effects of leading edge modifications on the post-stall characteristics of wings

NASA Technical Reports Server (NTRS)

Winkelmann, A. E.; Barlow, J. B.; Saini, J. K.; Anderson, J. D., Jr.; Jones, E.

1980-01-01

An investigation of the effects of leading edge modifications on the post-stall characteristics of two rectangular planform wings in a series of low speed wind tunnel tests is presented. Abrupt discontinuities in the leading edge shape of the wings were produced by placing a nose glove over a portion of the span or by deflecting sections of a segmented leading edge flap. Six component balance data, oil flow visualization photographs, and pressure distribution measurements were obtained, and tests made to study the development of flow separation at stall on small scale planform wing models. Results of oil flow visualization tests at and beyond stall showed the formation of counter-rotating swirl patterns on the upper surface of the '2-D' and '3-D' wings, and results of a numerical lifting line technique applied to wings with leading edge modifications are included.

Comorbidities confounding the outcomes of surgery for third window syndrome: Outlier analysis

PubMed Central

Mackay‐Promitas, Heather T.; Demirel, Shaban; Gianoli, Gerard J.; Gizzi, Martin S.; Carter, Dale M.; Siker, David A.

2017-01-01

Objective Patients with third window syndrome and superior semicircular canal dehiscence (SSCD) symptoms whose surgical outcomes placed them as outliers were systematically studied to determine comorbidities that were responsible for their poor outcomes due to these confounding factors. Study Design Observational analytic case‐control study in a tertiary referral center. Methods Twelve adult patients with clinical SSCD syndrome underwent surgical management and had outcomes that did not resolve all of their subjective symptoms. In addition to one of the neurotologists, 2 neurologists (one specializing in migraine and the other a neuro‐ophthalmologist), and a psychologist clinician‐investigator completed comprehensive evaluations. Neuropsychology test batteries included: the Millon Behavioral Medicine Diagnostic; Patient Health Questionnaire (PHQ‐9) and Generalized Anxiety Disorder Screener (GAD‐7); Adverse Childhood Experiences Scale; the Wide Range Assessment of Memory and Learning, including the 3 domains of verbal memory, visual memory, and attention/concentration; Wechsler Adult Intelligence Scale; and the Delis‐Kaplan Executive Function System. The control cohort was comprised of 17 participants who previously underwent surgery for third window syndrome that resulted in the expected outcomes of resolution of their third window syndrome symptoms and cognitive dysfunction. Results There was a high rate of psychological comorbidity (n = 6) in the outlier cohort; multiple traumatic brain injuries were also a confounding element (n = 10). One patient had elevated cerebrospinal fluid (CSF) pressure requiring ventriculoperitoneal shunting to control the recurrence of dehiscence and one patient with a drug‐induced Parkinson‐like syndrome and idiopathic progressive neurological degenerative process. Conclusions Components of the Millon Behavioral Medicine Diagnostic, PHQ‐9 and GAD‐7 results suggest that these instruments would be useful as

The effect of activated carbon support surface modification on characteristics of carbon nanospheres prepared by deposition precipitation of Fe-catalyst

NASA Astrophysics Data System (ADS)

Kristianto, H.; Arie, A. A.; Susanti, R. F.; Halim, M.; Lee, J. K.

2016-11-01

In this study the effect of activated carbon support modification to synthesis of CNSs was observed. Modification of activated carbon was done by using nitric acid. The effect of modification was analyzed from its FTIR spectra. The Fe catalysts were deposited on to the support by using urea deposition precipitation method at various initial catalysts concentration. CNSs was synthesized by utilizing cooking palm oil as renewable carbon source, and pyrolized at 700°C for 1 hour under nitrogen atmosphere. The products obtained then analyzed using SEM-EDS, TEM, XRD, and Raman spectroscopy. The modification of activated carbon support had increased the oxygen functional group. This increase resulted on increase of metal catalysts deposited on activated carbon surface. Peak of C (100) was observed, while ID/IG of samples were obtained around 0.9, which is commonly obtained for CNSs. High catalysts loading on modified activated carbon support caused decomposition of CNSs and formation carbon onion.

Estimation of mutagenic effect and modifications of mitosis by silver nanoparticles.

PubMed

Prokhorova, I M; Kibrik, B S; Pavlov, A V; Pesnya, D S

2013-12-01

We analyzed mutagenic and mitosis-modifying effects of silver nanoparticles (Allium test). Chromosome aberrations and laggings and micronuclei were simultaneously registered in the same sample. Mitotic and phase indexes were calculated. No mutagenic effects were detected after treatment with silver nanoparticles in doses of 1.0, 2.5, 5.0, and 50 mg/liter. Silver nanoparticles in a concentration of 50 mg/liter significantly increased the mitotic index. Nanoparticles in a dose of 5 mg/liter induced slight, but significant increase in mitotic index, but did not affect the ratio of phase indexes. Exposure to silver nanoparticles in concentrations of 1.0 and 2.5 mg/liter was not followed by modification of mitosis.

Effects of Selenylation Modification on Immune-Enhancing Activity of Garlic Polysaccharide

PubMed Central

Qin, Tao; Hu, Yuanliang; Wang, Deyun; Fan, Qiang; Zhang, Cunshuai; Chen, Xingying; Chen, Xiaolan; Liu, Cui; Gao, Zhenzhen; Li, Xiuping

2014-01-01

The garlic polysaccharide was modified by HNO3-Na2SeO3 method according to orthogonal design L9(34) to obtain nine selenizing garlic polysaccharides, sGPS1-sGPS9. Their effects on chicken peripheral lymphocytes proliferation in vitro were compared by MTT assay. The results showed that sGPSs could significantly promote lymphocytes proliferation, sGPS3, sGPS5 and sGPS6 presented stronger efficacy. In vivo experiment, 14-day-old chickens were injected respectively with sGPS3, sGPS5 and sGPS6 when they were vaccinated with ND vaccine taking unmodified GPS as control. The results showed that three sGPSs could significantly promote lymphocyte proliferation, enhance serum antibody titer, IFN-γ and IL-2 contents. These results indicated that selenylation modification could significantly enhance the immune-enhancing activity of GPS, sGPS6 possessed the best efficacy and could be as a candidate drug of immunoenhancer. Its optimal modification conditions were 400 mg of sodium selenite for 500 mg of GPS, reaction temperature of 70°C and reaction time of 6 h. PMID:24497946

Effects of selenylation modification on immune-enhancing activity of garlic polysaccharide.

PubMed

Qiu, Shulei; Chen, Jin; Qin, Tao; Hu, Yuanliang; Wang, Deyun; Fan, Qiang; Zhang, Cunshuai; Chen, Xingying; Chen, Xiaolan; Liu, Cui; Gao, Zhenzhen; Li, Xiuping

2014-01-01

The garlic polysaccharide was modified by HNO3-Na2SeO3 method according to orthogonal design L9(3(4)) to obtain nine selenizing garlic polysaccharides, sGPS1-sGPS9. Their effects on chicken peripheral lymphocytes proliferation in vitro were compared by MTT assay. The results showed that sGPSs could significantly promote lymphocytes proliferation, sGPS3, sGPS5 and sGPS6 presented stronger efficacy. In vivo experiment, 14-day-old chickens were injected respectively with sGPS3, sGPS5 and sGPS6 when they were vaccinated with ND vaccine taking unmodified GPS as control. The results showed that three sGPSs could significantly promote lymphocyte proliferation, enhance serum antibody titer, IFN-γ and IL-2 contents. These results indicated that selenylation modification could significantly enhance the immune-enhancing activity of GPS, sGPS6 possessed the best efficacy and could be as a candidate drug of immunoenhancer. Its optimal modification conditions were 400 mg of sodium selenite for 500 mg of GPS, reaction temperature of 70°C and reaction time of 6 h.

Effect of surface modification on carbon nanotubes (CNTs) catalyzed nitrobenzene reduction by sulfide.

PubMed

Liu, Qi; Zhao, Han-Qing; Li, Lei; He, Pan-Pan; Wang, Yi-Xuan; Yang, Hou-Yun; Hu, Zhen-Hu; Mu, Yang

2018-06-04

Carbon nanotubes (CNTs) could be directly used as metal-free catalysts for the reduction of nitroaromatics by sulfide in water, but their catalytic ability need a further improvement. This study evaluated the feasibility of surface modification through thermal and radiation pretreatments to enhance catalytic activity of CNTs on nitrobenzene reduction by sulfide. The results show that thermal treatment could effectively improve the catalytic behaviors of CNTs for the reduction of nitrobenzene by sulfide, where the optimum annealing temperature was 400 °C. However, plasma radiation pretreatment didn't result in an obvious improvement of the CNTs catalytic activity. Moreover, the possible reasons have been explored and discussed in the study. Additionally, the impacts of various operational parameters on nitrobenzene reduction catalyzed by the CNTs after an optimized surface modification were also evaluated. It was found that the rate of nitrobenzene removal by sulfide was positively correlated with CNTs doses in a range of 0.3-300 mg L -1 ; the optimum pH was around 8.0; higher temperature and sulfide concentration facilitated the reaction; and the presence of humic acid exhibited a negative effect on nitrobenzene reduction. Copyright © 2018 Elsevier B.V. All rights reserved.

'Mechanical restraint-confounders, risk, alliance score': testing the clinical validity of a new risk assessment instrument.

PubMed

Deichmann Nielsen, Lea; Bech, Per; Hounsgaard, Lise; Alkier Gildberg, Frederik

2017-08-01

Unstructured risk assessment, as well as confounders (underlying reasons for the patient's risk behaviour and alliance), risk behaviour, and parameters of alliance, have been identified as factors that prolong the duration of mechanical restraint among forensic mental health inpatients. To clinically validate a new, structured short-term risk assessment instrument called the Mechanical Restraint-Confounders, Risk, Alliance Score (MR-CRAS), with the intended purpose of supporting the clinicians' observation and assessment of the patient's readiness to be released from mechanical restraint. The content and layout of MR-CRAS and its user manual were evaluated using face validation by forensic mental health clinicians, content validation by an expert panel, and pilot testing within two, closed forensic mental health inpatient units. The three sub-scales (Confounders, Risk, and a parameter of Alliance) showed excellent content validity. The clinical validations also showed that MR-CRAS was perceived and experienced as a comprehensible, relevant, comprehensive, and useable risk assessment instrument. MR-CRAS contains 18 clinically valid items, and the instrument can be used to support the clinical decision-making regarding the possibility of releasing the patient from mechanical restraint. The present three studies have clinically validated a short MR-CRAS scale that is currently being psychometrically tested in a larger study.

Ubiquitin modifications

PubMed Central

Swatek, Kirby N; Komander, David

2016-01-01

Protein ubiquitination is a dynamic multifaceted post-translational modification involved in nearly all aspects of eukaryotic biology. Once attached to a substrate, the 76-amino acid protein ubiquitin is subjected to further modifications, creating a multitude of distinct signals with distinct cellular outcomes, referred to as the 'ubiquitin code'. Ubiquitin can be ubiquitinated on seven lysine (Lys) residues or on the N-terminus, leading to polyubiquitin chains that can encompass complex topologies. Alternatively or in addition, ubiquitin Lys residues can be modified by ubiquitin-like molecules (such as SUMO or NEDD8). Finally, ubiquitin can also be acetylated on Lys, or phosphorylated on Ser, Thr or Tyr residues, and each modification has the potential to dramatically alter the signaling outcome. While the number of distinctly modified ubiquitin species in cells is mind-boggling, much progress has been made to characterize the roles of distinct ubiquitin modifications, and many enzymes and receptors have been identified that create, recognize or remove these ubiquitin modifications. We here provide an overview of the various ubiquitin modifications present in cells, and highlight recent progress on ubiquitin chain biology. We then discuss the recent findings in the field of ubiquitin acetylation and phosphorylation, with a focus on Ser65-phosphorylation and its role in mitophagy and Parkin activation. PMID:27012465

Soil modification by invasive plants: Effects on native and invasive species of mixed-grass prairies

USGS Publications Warehouse

Jordan, N.R.; Larson, D.L.; Huerd, S.C.

2008-01-01

Invasive plants are capable of modifying attributes of soil to facilitate further invasion by conspecifics and other invasive species. We assessed this capability in three important plant invaders of grasslands in the Great Plains region of North America: leafy spurge (Euphorbia esula), smooth brome (Bromus inermis) and crested wheatgrass (Agropyron cristatum). In a glasshouse, these three invasives or a group of native species were grown separately through three cycles of growth and soil conditioning in both steam-pasteurized and non-pasteurized soils, after which we assessed seedling growth in these soils. Two of the three invasive species, Bromus and Agropyron, exhibited significant self-facilitation via soil modification. Bromus and Agropyron also had significant facilitative effects on other invasives via soil modification, while Euphorbia had significant antagonistic effects on the other invasives. Both Agropyron and Euphorbia consistently suppressed growth of two of three native forbs, while three native grasses were generally less affected. Almost all intra- and interspecific effects of invasive soil conditioning were dependent upon presence of soil biota from field sites where these species were successful invaders. Overall, these results suggest that that invasive modification of soil microbiota can facilitate plant invasion directly or via 'cross-facilitation' of other invasive species, and moreover has potential to impede restoration of native communities after removal of an invasive species. However, certain native species that are relatively insensitive to altered soil biota (as we observed in the case of the forb Linum lewisii and the native grasses), may be valuable as 'nurse'species in restoration efforts. ?? 2007 Springer Science+Business Media B.V.

Effects of electrode modification using calcium on the performance of alternating current field-induced polymer electroluminescent devices

NASA Astrophysics Data System (ADS)

Xia, Yingdong; Chen, Yonghua; Smith, Gregory M.; Li, Yuan; Huang, Wenxiao; Carroll, David L.

2013-06-01

In this work, the effects of electrode modification by calcium (Ca) on the performance of AC field induced polymer electroluminescence (FIPEL) devices are studied. The FIPEL device with Ca/Al electrode exhibits 550 cd m-2, which is 27.5 times higher than that of the device with only an Al electrode (20 cd m-2). Both holes and electrons are injected from one electrode in our FIPEL device. We found that the electron injection can be significantly enhanced by a Ca modification on the Al electrode without greatly affecting the hole injection. Therefore, the electrons and holes can be effectively recombined in the emissive layer to form more excitons under the AC voltage, leading to effective light emission. The device emitted much brighter light than other AC-based organic EL devices. This result provides an easy and effective way to improve FIPEL performance.

Mn-modification effects on Nb2O5 structural, optical and vibrational properties

NASA Astrophysics Data System (ADS)

Raba, A. M.; Murillo, E.; Joya, M. R.

2017-12-01

In this study Mn-modification (at 1%, 2.5%, 5% and 10%) on Nb2O5 was carried out through the Pechini method; the annealing temperatures: 400°C, 500°C, 600°C and 700°C, were used to study the thermal stability of the system and the crystalline growth. The crystallization at high temperatures has been investigated because low annealing temperature cannot improve the crystallization and the effect of Mn-modification concentration is worthy of a further investigation. Before annealing the samples were analysed by TGA. The structural analysis through XRD is carried out to study a possible increase of the crystallite size (L) by increasing the Mn concentration; for the samples at 700°C and 1% and 2.5% concentrations, L is increased from 39.81 to 46.45nm while L changes from 32.67 to 35.63 with 5% and 10%, respectively. After Mn-modification the evolution of (100) and (180) peaks Nb2O5 was observed suggesting that they were well defined only until 2.5%. IR and Raman spectroscopies allowed to analyse vibrational modes present in the samples: the IR spectrums for the samples at 400°C, 500°C and 600°C showed a band around 1100cm-1 which can be associated to C-C(νC-C) and C-O(νC-O) vibrations; at 700°C the shoulder was distinguished around 750cm-1 characteristics of the Nb2O5 orthorhombic structure. Vibration modes associated with Nb2O5 were found with the Raman spectroscopy; these become less intense after Mn-modification. The band gap energy was obtained through UV-Vis spectrophotometry which revealed a slight increase at 700°C.

Photoluminescence of CuInS2 nanocrystals: effect of surface modification

NASA Astrophysics Data System (ADS)

Kim, Young-Kuk; Cho, Young-Sang; Chung, Kookchae; Choi, Chul-Jin

2011-09-01

We have synthesized highly luminescent Cu-In-S(CIS) nanocrystals (NCs) by heating the mixture of metal carboxylates and alkylthiol under inert atmosphere. We modified the surface of CIS NCs with zinc carboxylate and subsequent injection of alkylthiol. As a result of the surface modification, highly luminescent CIS@ZnS core/shell nanocrystals were synthesized. The luminescence quantum yield (QY) of best CIS@ZnS NCs was above 50%, which is 10 times higher than the initial QY of CIS NCs before surface modification (QY=3%). Detailed study on the luminescence mechanism implies that etching of the surface of NCs by dissociated carboxylate group (CH3COO-) and formation of epitaxial shell by Zn with sulfur from alkylthiol efficiently removed the surface defects which are known to be major non-radiative recombination sites in semiconductor nanocrystals. In this study, we developed a novel surface modification route for monodispersed highly luminescent Cu-In-S NCs with less toxic and highly stable precursors. Investigation with the timeand the temperature-dependent photoluminescence showed that the trap related emission was minimized by surface modification and the donor-acceptor pair recombination was enhanced by controlling copper stoichiometry.xb

Are attractive men's faces masculine or feminine? The importance of controlling confounds in face stimuli.

PubMed

DeBruine, Lisa M; Jones, Benedict C; Smith, Finlay G; Little, Anthony C

2010-06-01

Women's preferences for male masculinity are highly variable. Although many researchers explain this variability as reflecting systematic individual differences in how women resolve the tradeoff between the costs and benefits of choosing a masculine partner, others suggest that methodological differences between studies are responsible. A recent study found general femininity preferences for judgments of faces that were manipulated in sexual dimorphism of shape but general masculinity preferences for judgments of faces that were based on perceived masculinity. Using the original stimuli, we replicated these previous results but found equivalent general femininity preferences for both types of faces when nonface confounds in the stimuli (e.g. hairstyle) were eliminated through masking. We conclude that care must be taken to control potential confounds in stimuli and that the influence of nonface cues on preferences for facial masculinity deserves further study.

The effect of different collagen modifications for titanium and titanium nitrite surfaces on functions of gingival fibroblasts.

PubMed

Ritz, U; Nusselt, T; Sewing, A; Ziebart, T; Kaufmann, K; Baranowski, A; Rommens, P M; Hofmann, Alexander

2017-01-01

Targeted modifications of the bulk implant surfaces using bioactive agents provide a promising tool for improvement of the long-term bony and soft tissue integration of dental implants. In this study, we assessed the cellular responses of primary human gingival fibroblasts (HGF) to different surface modifications of titanium (Ti) and titanium nitride (TiN) alloys with type I collagen or cyclic-RGDfK-peptide in order to define a modification improving long-term implants in dental medicine. Employing Ti and TiN implants, we compared the performance of simple dip coating and anodic immobilization of type I collagen that provided collagen layers of two different thicknesses. HGF were seeded on the different coated implants, and adhesion, proliferation, and gene expression were analyzed. Although there were no strong differences in initial cell adhesion between the groups at 2 and 4 hours, we found that all surface modifications induced higher proliferation rates as compared to the unmodified controls. Consistently, gene expression levels of cell adhesion markers (focal adhesion kinase (FAK), integrin beta1, and vinculin), cell differentiation markers (FGFR1, TGFb-R1), extracellular protein markers (type I collagen, vimentin), and cytoskeletal protein marker aktinin-1 were consistently higher in all surface modification groups at two different time points of investigation as compared to the unmodified controls. Our results indicate that simple dip coating of Ti and TiN with collagen is sufficient to induce in vitro cellular responses that are comparable to those of more reliable coating methods like anodic adsorption, chemical cross-linking, or RGD coating. TiN alloys do not possess any positive or adverse effects on HGF. Our results demonstrate a simple, yet effective, method for collagen coating on titanium implants to improve the long term integration and stability of dental implants.

Treating Retentive Encopresis: Dietary Modification and Behavioral Techniques.

ERIC Educational Resources Information Center

Nabors, Laura; Morgan, Sam B.

1995-01-01

A home-based contingency management program, consisting of diet modification, laxatives, correction for soiling accidents, stimulus control training, and positive reinforcement, was implemented for treatment of a 4-year-old encopretic male. The findings provide evidence supporting the effectiveness of dietary modification combined with behavior…

Position-dependent performance of copper phthalocyanine based field-effect transistors by gold nanoparticles modification.

PubMed

Luo, Xiao; Li, Yao; Lv, Wenli; Zhao, Feiyu; Sun, Lei; Peng, Yingquan; Wen, Zhanwei; Zhong, Junkang; Zhang, Jianping

2015-01-21

A facile fabrication and characteristics of copper phthalocyanine (CuPc)-based organic field-effect transistor (OFET) using the gold nanoparticles (Au NPs) modification is reported, thereby achieving highly improved performance. The effect of Au NPs located at three different positions, that is, at the SiO2/CuPc interface (device B), embedding in the middle of CuPc layer (device C), and on the top of CuPc layer (device D), is investigated, and the results show that device D has the best performance. Compared with the device without Au NPs (reference device A), device D displays an improvement of field-effect mobility (μ(sat)) from 1.65 × 10(-3) to 5.51 × 10(-3) cm(2) V(-1) s(-1), and threshold voltage decreases from -23.24 to -16.12 V. Therefore, a strategy for the performance improvement of the CuPc-based OFET with large field-effect mobility and saturation drain current is developed, on the basis of the concept of nanoscale Au modification. The model of an additional electron transport channel formation by FET operation at the Au NPs/CuPc interface is therefore proposed to explain the observed performance improvement. Optimum CuPc thickness is confirmed to be about 50 nm in the present study. The device-to-device uniformity and time stability are discussed for future application.

Determining confounding sensitivities in eddy current thin film measurements

NASA Astrophysics Data System (ADS)

Gros, Ethan; Udpa, Lalita; Smith, James A.; Wachs, Katelyn

2017-02-01

Eddy current (EC) techniques are widely used in industry to measure the thickness of non-conductive films on a metal substrate. This is done by using a system whereby a coil carrying a high-frequency alternating current is used to create an alternating magnetic field at the surface of the instrument's probe. When the probe is brought near a conductive surface, the alternating magnetic field will induce ECs in the conductor. The substrate characteristics and the distance of the probe from the substrate (the coating thickness) affect the magnitude of the ECs. The induced currents load the probe coil affecting the terminal impedance of the coil. The measured probe impedance is related to the lift off between coil and conductor as well as conductivity of the test sample. For a known conductivity sample, the probe impedance can be converted into an equivalent film thickness value. The EC measurement can be confounded by a number of measurement parameters. It was the goal of this research to determine which physical properties of the measurement set-up and sample can adversely affect the thickness measurement. The eddy-current testing was performed using a commercially available, hand-held eddy-current probe (ETA3.3H spring-loaded eddy probe running at 8 MHz) that comes with a stand to hold the probe. The stand holds the probe and adjusts the probe on the z-axis to help position the probe in the correct area as well as make precise measurements. The signal from the probe was sent to a hand-held readout, where the results are recorded directly in terms of liftoff or film thickness. Understanding the effect of certain factors on the measurements of film thickness, will help to evaluate how accurate the ETA3.3H spring-loaded eddy probe was at measuring film thickness under varying experimental conditions. This research studied the effects of a number of factors such as i) conductivity, ii) edge effect, iii) surface finish of base material and iv) cable condition.

Missing variables: how exclusion of human resources policy information confounds research connecting health and business outcomes.

PubMed

Lynch, Wendy D; Sherman, Bruce W

2014-01-01

When corporate health researchers examine the effects of health on business outcomes or the effect of health interventions on health and business outcomes, results will necessarily be confounded by the corporate environment(s) in which they are studied. In this research setting, most studies control for factors traditionally identified in public health, such as demographics and health status. Nevertheless, often overlooked is the extent to which company policies can also independently impact health care cost, work attendance, and productivity outcomes. With changes in employment and benefits practices resulting from health care reform, including incentives and plan design options, consideration of these largely neglected variables in research design has become increasingly important. This commentary summarizes existing knowledge regarding the implications of policy variations in research outcomes and provides a framework for incorporating them into future employer-based research.

Interpreting large-scale experiments on effects of trawling on benthic fauna: an empirical test of the potential effects of spatial confounding in experiments without replicated control and trawled areas.

PubMed

Lindegarth; Valentinsson; Hansson; Ulmestrand

2000-03-15

Disturbances due to trawling and dredging is a serious threat to assemblages of benthic marine animals. We tested hypotheses about effects of trawling on benthic assemblages in a manipulative field experiment, using gear and intensities relevant to future management of trawling in a Swedish fjord. Three trawled and three control sites were sampled at several times before and after trawling was initiated. This paper describes how conclusions about effects of trawling might differ between experiments involving replicate sites and experiments using only one trawled and one control site, as in several recent studies. Analyses of selected taxa showed that abundances of many species changed differently among control sites. Differences in temporal change between pairs of single trawled and control sites were also frequent. Neither the quantitative nor the qualitative nature of differences between treatments could, however, be coherently interpreted among the different combinations of trawled and control sites. This is consistent with results obtained from analyses using all sites, which showed no consistent effects of trawling on any of these taxa. These results provide empirical evidence that spatial confounding may cause serious problems to formal interpretation of experiments, which use only one control and one trawled area. Such potential problems can best be solved by ensuring that the study incorporates more than one control site.

Pseudouridine and N6-methyladenosine modifications weaken PUF protein/RNA interactions

PubMed Central

AlSadhan, Ishraq; Merriman, Dawn K.; Al-Hashimi, Hashim M.; Herschlag, Daniel

2017-01-01

RNA modifications are ubiquitous in biology, with over 100 distinct modifications. While the vast majority were identified and characterized on abundant noncoding RNA such as tRNA and rRNA, the advent of sensitive sequencing-based approaches has led to the discovery of extensive and regulated modification of eukaryotic messenger RNAs as well. The two most abundant mRNA modifications—pseudouridine (Ψ) and N6-methyladenosine (m6A)—affect diverse cellular processes including mRNA splicing, localization, translation, and decay and modulate RNA structure. Here, we test the hypothesis that RNA modifications directly affect interactions between RNA-binding proteins and target RNA. We show that Ψ and m6A weaken the binding of the human single-stranded RNA binding protein Pumilio 2 (hPUM2) to its consensus motif, with individual modifications having effects up to approximately threefold and multiple modifications giving larger effects. While there are likely to be some cases where RNA modifications essentially fully ablate protein binding, here we see modest responses that may be more common. Such modest effects could nevertheless profoundly alter the complex landscape of RNA:protein interactions, and the quantitative rather than qualitative nature of these effects underscores the need for quantitative, systems-level accounting of RNA:protein interactions to understand post-transcriptional regulation. PMID:28138061

Examining confounding by diet in the association between perfluoroalkyl acids and serum cholesterol in pregnancy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skuladottir, Margret; Ramel, Alfons; Unit for Nutrition Research, Landspitali National University Hospital, Reykjavik

Background: Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have consistently been associated with higher cholesterol levels in cross sectional studies. Concerns have, however, been raised about potential confounding by diet and clinical relevance. Objective: To examine the association between concentrations of PFOS and PFOA and total cholesterol in serum during pregnancy taking into considerations confounding by diet. Methods: 854 Danish women who gave birth in 1988–89 and provided a blood sample and reported their diet in week 30 of gestation. Results: Mean serum PFOS, PFOA and total cholesterol concentrations were 22.3 ng/mL, 4.1 ng/mL and 7.3 mmol/L, respectively. Maternal dietmore » was a significant predictor of serum PFOS and PFOA concentrations. In particular intake of meat and meat products was positively associated while intake of vegetables was inversely associated (P for trend <0.01) with relative difference between the highest and lowest quartile in PFOS and PFOA concentrations ranging between 6% and 25% of mean values. After adjustment for dietary factors both PFOA and PFOS were positively and similarly associated with serum cholesterol (P for trend ≤0.01). For example, the mean increase in serum cholesterol was 0.39 mmol/L (95%CI: 0.09, 0.68) when comparing women in the highest to lowest quintile of PFOA concentrations. In comparison the mean increase in serum cholesterol was 0.61 mmol/L (95%CI: 0.17, 1.05) when comparing women in the highest to lowest quintile of saturated fat intake. Conclusion: In this study associations between PFOS and PFOA with serum cholesterol appeared unrelated to dietary intake and were similar in magnitude as the associations between saturated fat intake and serum cholesterol. - Highlights: • PFOS and PFOA have consistently been linked with raised serum cholesterol • Clinical relevance remains uncertain and confounding by diet has been suggested • The aim of this study was to address these

Manufacturer evaluations of endograft modifications.

PubMed

Waninger, Matthew S; Whirley, Robert G; Smith, Louis J; Wolf, Ben S

2013-03-01

The motivation to modify the design of a vascular device can arise from a number of sources. Clinical experience with the unmodified device could suggest new design modifications to improve device performance or clinical outcomes. Similarly, clinical success with a device often suggests modifications that could broaden the applicability of the device to enable treatment of different or more advanced disease states. As a specific example, both of these scenarios have arisen during the last decade in the evolution of endovascular grafts for the treatment of abdominal aortic aneurysms, with modifications enabling the treatment of patients with shorter infrarenal necks, more angulated anatomy, and smaller access vessels. These modifications have been made by manufacturers and additionally by physicians who create branched and fenestrated devices. The experience to date with the use of fenestrated devices and the development of chimney, snorkel, and periscope techniques suggests that modifications to off-the-shelf devices may provide some clinical benefit. This experience provides additional motivation for manufacturers to develop devices to address the clinical needs not met with their current product lines. For manufacturers, the device development process includes an assessment of the new device design to determine the appropriate evaluation strategy to support the safety and effectiveness of the modified device. This report provides a high-level overview of the process generally followed by device manufacturers to evaluate a proposed device modification before market release, in accordance with local country regulations and recognized international standards such as the International Organization of Standardization (ISO) standards for endovascular grafts (ISO 25539 Part 1). Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

PERMANOVA-S: association test for microbial community composition that accommodates confounders and multiple distances.

PubMed

Tang, Zheng-Zheng; Chen, Guanhua; Alekseyenko, Alexander V

2016-09-01

Recent advances in sequencing technology have made it possible to obtain high-throughput data on the composition of microbial communities and to study the effects of dysbiosis on the human host. Analysis of pairwise intersample distances quantifies the association between the microbiome diversity and covariates of interest (e.g. environmental factors, clinical outcomes, treatment groups). In the design of these analyses, multiple choices for distance metrics are available. Most distance-based methods, however, use a single distance and are underpowered if the distance is poorly chosen. In addition, distance-based tests cannot flexibly handle confounding variables, which can result in excessive false-positive findings. We derive presence-weighted UniFrac to complement the existing UniFrac distances for more powerful detection of the variation in species richness. We develop PERMANOVA-S, a new distance-based method that tests the association of microbiome composition with any covariates of interest. PERMANOVA-S improves the commonly-used Permutation Multivariate Analysis of Variance (PERMANOVA) test by allowing flexible confounder adjustments and ensembling multiple distances. We conducted extensive simulation studies to evaluate the performance of different distances under various patterns of association. Our simulation studies demonstrate that the power of the test relies on how well the selected distance captures the nature of the association. The PERMANOVA-S unified test combines multiple distances and achieves good power regardless of the patterns of the underlying association. We demonstrate the usefulness of our approach by reanalyzing several real microbiome datasets. miProfile software is freely available at https://medschool.vanderbilt.edu/tang-lab/software/miProfile z.tang@vanderbilt.edu or g.chen@vanderbilt.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

PERMANOVA-S: association test for microbial community composition that accommodates confounders and multiple distances

PubMed Central

Tang, Zheng-Zheng; Chen, Guanhua; Alekseyenko, Alexander V.

2016-01-01

Motivation: Recent advances in sequencing technology have made it possible to obtain high-throughput data on the composition of microbial communities and to study the effects of dysbiosis on the human host. Analysis of pairwise intersample distances quantifies the association between the microbiome diversity and covariates of interest (e.g. environmental factors, clinical outcomes, treatment groups). In the design of these analyses, multiple choices for distance metrics are available. Most distance-based methods, however, use a single distance and are underpowered if the distance is poorly chosen. In addition, distance-based tests cannot flexibly handle confounding variables, which can result in excessive false-positive findings. Results: We derive presence-weighted UniFrac to complement the existing UniFrac distances for more powerful detection of the variation in species richness. We develop PERMANOVA-S, a new distance-based method that tests the association of microbiome composition with any covariates of interest. PERMANOVA-S improves the commonly-used Permutation Multivariate Analysis of Variance (PERMANOVA) test by allowing flexible confounder adjustments and ensembling multiple distances. We conducted extensive simulation studies to evaluate the performance of different distances under various patterns of association. Our simulation studies demonstrate that the power of the test relies on how well the selected distance captures the nature of the association. The PERMANOVA-S unified test combines multiple distances and achieves good power regardless of the patterns of the underlying association. We demonstrate the usefulness of our approach by reanalyzing several real microbiome datasets. Availability and Implementation: miProfile software is freely available at https://medschool.vanderbilt.edu/tang-lab/software/miProfile. Contact: z.tang@vanderbilt.edu or g.chen@vanderbilt.edu Supplementary information: Supplementary data are available at Bioinformatics

Clinical and evoked pain, personality traits, and emotional states: can familial confounding explain the associations?

PubMed

Strachan, Eric; Poeschla, Brian; Dansie, Elizabeth; Succop, Annemarie; Chopko, Laura; Afari, Niloofar

2015-01-01

Pain is a complex phenomenon influenced by context and person-specific factors. Affective dimensions of pain involve both enduring personality traits and fleeting emotional states. We examined how personality traits and emotional states are linked with clinical and evoked pain in a twin sample. 99 female twin pairs were evaluated for clinical and evoked pain using the McGill Pain Questionnaire (MPQ) and dolorimetry, and completed the 120-item International Personality Item Pool (IPIP), the Positive and Negative Affect Scale (PANAS), and ratings of stress and mood. Using a co-twin control design we examined a) the relationship of personality traits and emotional states with clinical and evoked pain and b) whether genetics and common environment (i.e. familial factors) may account for the associations. Neuroticism was associated with the sensory component of the MPQ; this relationship was not confounded by familial factors. None of the emotional state measures was associated with the MPQ. PANAS negative affect was associated with lower evoked pressure pain threshold and tolerance; these associations were confounded by familial factors. There were no associations between IPIP traits and evoked pain. A relationship exists between neuroticism and clinical pain that is not confounded by familial factors. There is no similar relationship between negative emotional states and clinical pain. In contrast, the relationship between negative emotional states and evoked pain is strong while the relationship with enduring personality traits is weak. The relationship between negative emotional states and evoked pain appears to be non-causal and due to familial factors. Copyright © 2014 Elsevier Inc. All rights reserved.

Diet Modification for Hyperlipidemia

PubMed Central

Mann, Heather D.; Piotrowski, Pamela

1992-01-01

Hyperlipidemia is a major risk factor associated with cardiovascular disease. Dietary modification is effective in achieving and maintaining improved serum lipid levels. Nutritional care provided by a dietitian includes individual dietary and lifestyle assessment, formulating an appropriate dietary regimen, education, and follow-up assessments. PMID:21221406

Cognitive Modification and Systematic Desensitization with Test Anxious High School Students.

ERIC Educational Resources Information Center

Leal, Lois L.; And Others

1981-01-01

Compares the relative effectiveness of cognitive modification and systematic desensitization with test anxious high school students (N=30). The systematic desensitization treatment appeared to be significantly more effective on the performance measure while cognitive modification was more effective on one of the self-report measures. (Author/JAC)

Chemical methods for encoding and decoding of posttranslational modifications

PubMed Central

Chuh, Kelly N.; Batt, Anna R.; Pratt, Matthew R.

2016-01-01

A large array of posttranslational modifications can dramatically change the properties of proteins and influence different aspects of their biological function such as enzymatic activity, binding interactions, and proteostasis. Despite the significant knowledge that has been gained about the function of posttranslational modifications using traditional biological techniques, the analysis of the site-specific effects of a particular modification, the identification of the full compliment of modified proteins in the proteome, and the detection of new types of modifications remains challenging. Over the years, chemical methods have contributed significantly in both of these areas of research. This review highlights several posttranslational modifications where chemistry-based approaches have made significant contributions to our ability to both prepare homogeneously modified proteins and identify and characterize particular modifications in complex biological settings. As the number and chemical diversity of documented posttranslational modifications continues to rise, we believe that chemical strategies will be essential to advance the field in years to come. PMID:26933738

Is the Association of Subjective SES and Self-Rated Health Confounded by Negative Mood? An Experimental Approach

PubMed Central

Kraus, Michael W.; Adler, Nancy; David Chen, Teh-Way

2012-01-01

Objective Lower subjective socioeconomic status (SSS) consistently shows associations with poorer health with the strongest relationships emerging with global self-rated health. Though often interpreted as reflecting the impact of low SSS on health, the association could also arise from confounding SSS with negative affect. In this research we sought to determine if negative affect confounds, or alternatively, is on the causal pathway linking SSS to self-rated health. Methods 300 adult participants—recruited from throughout the United States—were randomized to experience sadness, shame, or a neutral mood induction wherein they wrote about and visualized a particularly emotionally evocative event. Participants subsequently completed measures of SSS, self-rated health, depression, and negative mood. Results Consistent with predictions, neither SSS scores nor the association of SSS with self-rated health, depression, and chronic negative affect differed by mood induction condition, controlling for demographic factors that covary with SSS (e.g., age, gender, education, income). Moreover, chronic negative affect partially explained the relationship between SSS and self-rated health, independent of manipulated mood. Conclusions These findings support the utility of the measurement of SSS, and provide evidence suggesting that chronic negative affect is a likely mediator of the SSS association with global health rather than a confounder. PMID:22329426

Posttranslational modifications of Rab proteins cause effective displacement of GDP dissociation inhibitor.

PubMed

Oesterlin, Lena K; Goody, Roger S; Itzen, Aymelt

2012-04-10

Intracellular vesicular trafficking is regulated by approximately 60 members of the Rab subfamily of small Ras-like GDP/GTP binding proteins. Rab proteins cycle between inactive and active states as well as between cytosolic and membrane bound forms. Membrane extraction/delivery and cytosolic distribution of Rabs is mediated by interaction with the protein GDP dissociation inhibitor (GDI) that binds to prenylated inactive (GDP-bound) Rab proteins. Because the Rab:GDP:GDI complex is of high affinity, the question arises of how GDI can be displaced efficiently from Rab protein in order to allow the necessary recruitment of the Rab to its specific target membrane. While there is strong evidence that DrrA, as a bacterially encoded GDP/GTP exchange factor, contributes to this event, we show here that posttranslational modifications of Rabs can also modulate the affinity for GDI and thus cause effective displacement of GDI from Rab:GDI complexes. These activities have been found associated with the phosphocholination and adenylylation activities of the enzymes AnkX and DrrA/SidM, respectively, from the pathogenic bacterium Legionella pneumophila. Both modifications occur after spontaneous dissociation of Rab:GDI complexes within their natural equilibrium. Therefore, the effective GDI displacement that is observed is caused by inhibition of reformation of Rab:GDI complexes. Interestingly, in contrast to adenylylation by DrrA, AnkX can covalently modify inactive Rabs with high catalytic efficiency even when GDP is bound to the GTPase and hence can inhibit binding of GDI to Rab:GDP complexes. We therefore speculate that human cells could employ similar mechanisms in the absence of infection to effectively displace Rabs from GDI.

Behavior modification therapy in hyperactive children. Research and clinical implications.

PubMed

Wolraich, M L

1979-09-01

One hundred fifty-seven studies employing behavior modification in the management of hyperactive and disruptive children were reviewed. The studies were analyzed against standards of scientific validity. The review found: (1) behavior modification was effective in alleviating problem behaviors; (2) token programs were the most commonly used; (3) both positive reinforcement and punishment were effective; positive reinforcement, however, had the advantage of improving self-esteem; (4) behavioral problems occurring in the home most likely require a home-based program; (5) behavior modification and stimulant medication can be used simultaneously, often with additive effects; and (6) long-term benefits beyond one year have not been assessed.

Residual confounding explains the association between high parity and child mortality.

PubMed

Kozuki, Naoko; Sonneveldt, Emily; Walker, Neff

2013-01-01

This study used data from recent Demographic and Health Surveys (DHS) to examine the impact of high parity on under-five and neonatal mortality. The analyses used various techniques to attempt eliminating selection issues, including stratification of analyses by mothers' completed fertility. We analyzed DHS datasets from 47 low- and middle-income countries. We only used data from women who were age 35 or older at the time of survey to have a measure of their completed fertility. We ran log-binominal regression by country to calculate relative risk between parity and both under-five and neonatal mortality, controlled for wealth quintile, maternal education, urban versus rural residence, maternal age at first birth, calendar year (to control for possible time trends), and birth interval. We then controlled for maternal background characteristics even further by using mothers' completed fertility as a proxy measure. We found a statistically significant association between high parity and child mortality. However, this association is most likely not physiological, and can be largely attributed to the difference in background characteristics of mothers who complete reproduction with high fertility versus low fertility. Children of high completed fertility mothers have statistically significantly increased risk of death compared to children of low completed fertility mothers at every birth order, even after controlling for available confounders (i.e. among children of birth order 1, adjusted RR of under-five mortality 1.58, 95% CI: 1.42, 1.76). There appears to be residual confounders that put children of high completed fertility mothers at higher risk, regardless of birth order. When we examined the association between parity and under-five mortality among mothers with high completed fertility, it remained statistically significant, but negligible in magnitude (i.e. adjusted RR of under-five mortality 1.03, 95% CI: 1.02-1.05). Our analyses strongly suggest that the

Plant Sterols: Chemical and Enzymatic Structural Modifications and Effects on Their Cholesterol-Lowering Activity.

PubMed

He, Wen-Sen; Zhu, Hanyue; Chen, Zhen-Yu

2018-03-28

Plant sterols have attracted increasing attention due to their excellent cholesterol-lowering activity. However, free plant sterols have some characteristics of low oil solubility, water insolubility, high melting point, and low bioavailability, which greatly limit their application in foods. Numerous studies have been undertaken to modify their chemical structures to improve their chemical and physical properties in meeting the needs of various applications. The present review is to summarize the literature and update the progress on structural modifications of plant sterols in the following aspects: (i) synthesis of plant sterol esters by esterification and transesterification with hydrophobic fatty acids and triacylglycerols to improve their oil solubility, (ii) synthesis of plant sterol derivatives by coupling with various hydrophilic moieties to enhance their water solubility, and (iii) mechanisms by which plant sterols reduce plasma cholesterol and the effect of structural modifications on plasma cholesterol-lowering activity of plant sterols.

40 CFR 52.736 - Review of new sources and modifications.

Code of Federal Regulations, 2010 CFR

2010-07-01

... sources and modifications. (a) [Reserved] (b) The rules submitted by the State on March 24, 1988, to... Sources Construction and Modification as effective March 22, 1991. The moratorium on construction and...

Glycation of antibodies: Modification, methods and potential effects on biological functions.

PubMed

Wei, Bingchuan; Berning, Kelsey; Quan, Cynthia; Zhang, Yonghua Taylor

Glycation is an important protein modification that could potentially affect bioactivity and molecular stability, and glycation of therapeutic proteins such as monoclonal antibodies should be well characterized. Glycated protein could undergo further degradation into advance glycation end (AGE) products. Here, we review the root cause of glycation during the manufacturing, storage and in vivo circulation of therapeutic antibodies, and the current analytical methods used to detect and characterize glycation and AGEs, including boronate affinity chromatography, charge-based methods, liquid chromatography-mass spectrometry and colorimetric assay. The biological effects of therapeutic protein glycation and AGEs, which ranged from no affect to loss of activity, are also discussed.

Investigating the effects of in utero benzene exposure on epigenetic modifications in maternal and fetal CD-1 mice.

PubMed

Philbrook, Nicola A; Winn, Louise M

2015-11-15

Exposure to the ubiquitous environmental pollutant benzene is positively correlated with leukemia in adults and may be associated with childhood leukemia following in utero exposure. While numerous studies implicate oxidative stress and DNA damage as playing a role in benzene-mediated carcinogenicity, emerging evidence suggests that alterations in epigenetic regulations may be involved. The present study aimed to determine whether DNA methylation and/or various histone modifications were altered following in utero benzene exposure in CD-1 mice. Global DNA methylation and promoter-specific methylation of the tumor suppressor gene, p15, were assessed. Additionally, levels of acetylated histones H3, H4, and H3K56, as well as methylated histones H3K9 and H3K27 were assessed by Western blotting. A significant decrease in global DNA methylation of maternal bone marrow was observed following benzene exposure; however no effect on global DNA methylation was detected in fetal livers. Additionally, no effect of benzene exposure was observed on p15 promoter methylation or any measured histone modifications in both maternal bone marrow and fetal livers. These results suggest that the methodology used in the present study did not reveal alterations in DNA methylation and histone modifications following in utero exposure to benzene; however further experimentation investigating these modifications at the whole genome/epigenome level, as well as at later stages of benzene-induced carcinogenesis, are warranted. Copyright © 2015 Elsevier Inc. All rights reserved.

Handling stress may confound murine gut microbiota studies.

PubMed

Allen-Blevins, Cary R; You, Xiaomeng; Hinde, Katie; Sela, David A

2017-01-01

Accumulating evidence indicates interactions between human milk composition, particularly sugars (human milk oligosaccharides or HMO), the gut microbiota of human infants, and behavioral effects. Some HMO secreted in human milk are unable to be endogenously digested by the human infant but are able to be metabolized by certain species of gut microbiota, including Bifidobacterium longum subsp. infantis (B. infantis) , a species sensitive to host stress (Bailey & Coe, 2004). Exposure to gut bacteria like B. infantis during critical neurodevelopment windows in early life appears to have behavioral consequences; however, environmental, physical, and social stress during this period can also have behavioral and microbial consequences. While rodent models are a useful method for determining causal relationships between HMO, gut microbiota, and behavior, murine studies of gut microbiota usually employ oral gavage, a technique stressful to the mouse. Our aim was to develop a less-invasive technique for HMO administration to remove the potential confound of gavage stress. Under the hypothesis that stress affects gut microbiota, particularly B. infantis , we predicted the pups receiving a prebiotic solution in a less-invasive manner would have the highest amount of Bifidobacteria in their gut. This study was designed to test two methods, active and passive, of solution administration to mice and the effects on their gut microbiome. Neonatal C57BL/6J mice housed in a specific-pathogen free facility received increasing doses of fructooligosaccharide (FOS) solution or deionized, distilled water. Gastrointestinal (GI) tracts were collected from five dams, six sires, and 41 pups over four time points. Seven fecal pellets from unhandled pups and two pellets from unhandled dams were also collected. Qualitative real-time polymerase chain reaction (qRT-PCR) was used to quantify and compare the amount of Bifidobacterium , Bacteroides , Bacteroidetes, and Firmicutes. Our results

A weight modification sequential method for VSC-MTDC power system state estimation

NASA Astrophysics Data System (ADS)

Yang, Xiaonan; Zhang, Hao; Li, Qiang; Guo, Ziming; Zhao, Kun; Li, Xinpeng; Han, Feng

2017-06-01

This paper presents an effective sequential approach based on weight modification for VSC-MTDC power system state estimation, called weight modification sequential method. The proposed approach simplifies the AC/DC system state estimation algorithm through modifying the weight of state quantity to keep the matrix dimension constant. The weight modification sequential method can also make the VSC-MTDC system state estimation calculation results more ccurate and increase the speed of calculation. The effectiveness of the proposed weight modification sequential method is demonstrated and validated in modified IEEE 14 bus system.

Optimal Control Modification Adaptive Law for Time-Scale Separated Systems

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T.

2010-01-01

Recently a new optimal control modification has been introduced that can achieve robust adaptation with a large adaptive gain without incurring high-frequency oscillations as with the standard model-reference adaptive control. This modification is based on an optimal control formulation to minimize the L2 norm of the tracking error. The optimal control modification adaptive law results in a stable adaptation in the presence of a large adaptive gain. This study examines the optimal control modification adaptive law in the context of a system with a time scale separation resulting from a fast plant with a slow actuator. A singular perturbation analysis is performed to derive a modification to the adaptive law by transforming the original system into a reduced-order system in slow time. A model matching conditions in the transformed time coordinate results in an increase in the actuator command that effectively compensate for the slow actuator dynamics. Simulations demonstrate effectiveness of the method.

Mapping Base Modifications in DNA by Transverse-Current Sequencing

NASA Astrophysics Data System (ADS)

Alvarez, Jose R.; Skachkov, Dmitry; Massey, Steven E.; Kalitsov, Alan; Velev, Julian P.

2018-02-01

Sequencing DNA modifications and lesions, such as methylation of cytosine and oxidation of guanine, is even more important and challenging than sequencing the genome itself. The traditional methods for detecting DNA modifications are either insensitive to these modifications or require additional processing steps to identify a particular type of modification. Transverse-current sequencing in nanopores can potentially identify the canonical bases and base modifications in the same run. In this work, we demonstrate that the most common DNA epigenetic modifications and lesions can be detected with any predefined accuracy based on their tunneling current signature. Our results are based on simulations of the nanopore tunneling current through DNA molecules, calculated using nonequilibrium electron-transport methodology within an effective multiorbital model derived from first-principles calculations, followed by a base-calling algorithm accounting for neighbor current-current correlations. This methodology can be integrated with existing experimental techniques to improve base-calling fidelity.

Transcript Isoform Variation Associated with Cytosine Modification in Human Lymphoblastoid Cell Lines.

PubMed

Zhang, Xu; Zhang, Wei

2016-06-01

Cytosine modification on DNA is variable among individuals, which could correlate with gene expression variation. The effect of cytosine modification on interindividual transcript isoform variation (TIV), however, remains unclear. In this study, we assessed the extent of cytosine modification-specific TIV in lymphoblastoid cell lines (LCLs) derived from unrelated individuals of European and African descent. Our study detected cytosine modification-specific TIVs for 17% of the analyzed genes at a 5% false discovery rate. Forty-five percent of the TIV-associated cytosine modifications correlated with the overall gene expression levels as well, with the corresponding CpG sites overrepresented in transcript initiation sites, transcription factor binding sites, and distinct histone modification peaks, suggesting that alternative isoform transcription underlies the TIVs. Our analysis also revealed 33% of the TIV-associated cytosine modifications that affected specific exons, with the corresponding CpG sites overrepresented in exon/intron junctions, splicing branching points, and transcript termination sites, implying that the TIVs are attributable to alternative splicing or transcription termination. Genetic and epigenetic regulation of TIV shared target preference but exerted independent effects on 61% of the common exon targets. Cytosine modification-specific TIVs detected from LCLs were differentially enriched in those detected from various tissues in The Cancer Genome Atlas, indicating their developmental dependency. Genes containing cytosine modification-specific TIVs were enriched in pathways of cancers and metabolic disorders. Our study demonstrated a prominent effect of cytosine modification variation on the transcript isoform spectrum over gross transcript abundance and revealed epigenetic contributions to diseases that were mediated through cytosine modification-specific TIV. Copyright © 2016 by the Genetics Society of America.

Effect of dietary behaviour modification on anthropometric indices and eating behaviour in obese adolescent girls.

PubMed

Sabet Sarvestani, Raheleh; Jamalfard, Mohammad Hoseein; Kargar, Marziye; Kaveh, Mohammad Hoseein; Tabatabaee, Hamid Reza

2009-08-01

This paper is a report of a study conducted to evaluate the effects of behaviour modification on anthropometric indices and to explore if behaviour modification could improve eating behaviour in adolescents. Obesity is currently the most important nutritional disease of children and adolescents. To date, several attempts to achieve weight loss in children have been made, but little is known about their effects on improving eating behaviours. Sixty obese adolescent girls participated in a behaviour modification program which was held for 16 weeks in 2007. The participants were randomly selected from two different schools and were assigned to an experimental and control group (30 participants each). Anthropometric indices and eating behaviours were assessed before and after the program. Eating behaviour was assessed using the Dutch Eating Behaviour Questionnaire. There were statistically significant differences in changes in body weight (-2.75 kg vs. 0.62 kg), body mass index (-1.07 kg/m(2) vs. 0.24 kg/m(2)) and arm circumference (-2.31 cm vs. 0.5 cm) in the experimental group in contrast to controls (P < 0.001). There were also statistically significant differences in scores for eating behaviour, emotional eating (0.63, 0.17), external eating (0.99, 0.05) and restrained eating (0.72, 0.03) in the experimental vs. the control group respectively (P < 0.001). Nurses, more than other healthcare professionals, can address obesity in adolescents and they should not concentrate solely on weight reduction, but also encourage children to acquire a healthy lifestyle.

Meta-analysis of the independent and cumulative effects of multiple genetic modifications on pig lung xenograft performance during ex vivo perfusion with human blood

PubMed Central

Harris, Donald G.; Quinn, Kevin J.; French, Beth M.; Schwartz, Evan; Kang, Elizabeth; Dahi, Siamak; Phelps, Carol J.; Ayares, David L.; Burdorf, Lars; Azimzadeh, Agnes M.; Pierson, Richard N.

2014-01-01

Background Genetically modified pigs are a promising potential source of lung xenografts. Ex-vivo xenoperfusion is an effective platform for testing the effect of new modifications, but typical experiments are limited by testing of a single genetic intervention and small sample sizes. The purpose of this study was to analyze the individual and aggregate effects of donor genetic modifications on porcine lung xenograft survival and injury in an extensive pig lung xenoperfusion series. Methods Data from 157 porcine lung xenoperfusion experiments using otherwise unmodified heparinized human blood were aggregated as either continuous or dichotomous variables. Lungs were wild type in 17 perfusions (11% of the study group), while 31 lungs (20% of the study group) had 1 genetic modification, 40 lungs (39%) had 2, and 47 lungs (30%) had 3 or more modifications. The primary endpoint was functional lung survival to 4 hours of perfusion. Secondary analyses evaluated previously identified markers associated with known lung xenograft injury mechanisms. In addition to comparison among all xenografts grouped by survival status, a subgroup analysis was performed of lungs incorporating the GalTKO.hCD46 genotype. Results Each increase in the number of genetic modifications was associated with additional prolongation of lung xenograft survival. Lungs that exhibited survival to 4 hours generally had reduced platelet activation and thrombin generation. GalTKO and the expression of hCD46, HO-1, hCD55 or hEPCR were associated with improved survival. hTBM, HLA-E, and hCD39 were associated with no significant effect on the primary outcome. Conclusion This meta-analysis of an extensive lung xenotransplantation series demonstrates that increasing the number of genetic modifications targeting known xenogeneic lung injury mechanisms is associated with incremental improvements in lung survival. While more detailed mechanistic studies are needed to explore the relationship between gene expression

Desire thinking as a confounder in the relationship between mindfulness and craving: Evidence from a cross-cultural validation of the Desire Thinking Questionnaire.

PubMed

Chakroun-Baggioni, Nadia; Corman, Maya; Spada, Marcantonio M; Caselli, Gabriele; Gierski, Fabien

2017-10-01

Desire thinking and mindfulness have been associated with craving. The aim of the present study was to validate the French version of the Desire Thinking Questionnaire (DTQ) and to investigate the relationship between mindfulness, desire thinking and craving among a sample of university students. Four hundred and ninety six university students completed the DTQ and measures of mindfulness, craving and alcohol use. Results from confirmatory factor analyses showed that the two-factor structure proposed in the original DTQ exhibited suitable goodness-of-fit statistics. The DTQ also demonstrated good internal reliability, temporal stability and predictive validity. A set of linear regressions revealed that desire thinking had a confounding effect in the relationship between mindfulness and craving. The confounding role of desire thinking in the relationship between mindfulness and craving suggests that interrupting desire thinking may be a viable clinical option aimed at reducing craving. Copyright © 2017 Elsevier B.V. All rights reserved.

Cumulative effects of electrode and dielectric surface modifications on pentacene-based transistors

NASA Astrophysics Data System (ADS)

Devynck, Mélanie; Tardy, Pascal; Wantz, Guillaume; Nicolas, Yohann; Vellutini, Luc; Labrugère, Christine; Hirsch, Lionel

2012-01-01

Surface modifications of the dielectric and the metal of pentacene-based field effect transistors using self-assembled monolayer (SAM) were studied. First, a low interfacial trap density and pentacene 2D-growth were favored by the nonpolar and low surface energy of octadecyltrichlorosilane-based SAM. This treatment leaded to increased mobility up to 0.4 cm2 V-1 s-1 and no observable hysteresis on transfer curves. Second, reduced hole injection barrier and contact resistance were achieved by fluorinated thiols deposited on gold contacts resulting in an increased mobility up to 0.6 cm2 V-1 s-1. Finally, a high mobility of 2.6 cm2 V-1 s-1 was achieved by cumulative effects of both treatments.

Ground cloud related weather modification effects. [heavy lift launch vehicles

NASA Technical Reports Server (NTRS)

Lee, J.

1980-01-01

The principal concerns about inadvertent weather modification by the solar power satellite system rocket effluents are discussed, namely the possibility that the ground cloud might temporarily modify local weather and the cumulative effects of nearly 500 launches per year. These issues are discussed through the consideration of (1) the possible alteration of the microphysical processes of clouds in the general area due to rocket effluents and debris and cooling water entrained during the launch and (2) the direct dynamical and thermodynamical responses to the inputs of thermal energy and moisture from the rocket exhaust for given ambient meteorological conditions. The huge amount of thermal energy contained in the exhaust of the proposed launch vehicle would in some situations induce a saturated, wet convective cloud or enhance an existing convective activity. Nevertheless, the effects would be limited to the general area of the launch site. The observed long lasting high concentrations of cloud condensation nuclei produced during and after a rocket launch may appreciably affect the frequency of occurrence and persistence of fogs and haze. In view of the high mission frequency proposed for the vehicle launches, a potential exists for a cumulative effect.

[Educational effectiveness of a group health education program in the workplace and an examination of educational methods to promote behavior modification].

PubMed

Kageyama, Makoto; Odagiri, Keiichi; Suzuki, Naoko; Honda, Kumiko; Onoue, Kazue; Yamamoto, Makoto; Mizuta, Isagi; Uehara, Akihiko

2014-01-01

It is well-known that health education programs carried out in the work place are useful for employees' health promotion. However, the effectiveness of group health education programs for workers as a population approach is unclear. The purpose of this study was to examine the effectiveness of a group health education program in the workplace, and to investigate educational methods which support workers modifying their health behaviors. A total of 289 workers who received a group health education program in the manufacturing industry (mean age, 42.1 ± 11.3 years old; 175 males and 114 females) were enrolled in this study. The group health education program was carried out to educate the subjects about periodontitis, oral health actions and lifestyle behaviors to prevent oral diseases. Participants were required to fill out a self-administered questionnaire which included information about oral health knowledge, oral health actions, lifestyle behaviors and symptoms of periodontitis before, immediately after and one month after the education. We used McNemar's test for the paired comparison of questionnaire responses. The relation between acquiring knowledge about periodontitis and subjects' modification of oral health action, behavior modification and symptoms of periodontitis were examined using the chi-squared test. The relationships of knowledge retention about periodontitis, the modification of the oral health actions and lifestyle behaviors (i.e., cigarette smoking, alcohol drinking and eating between meals), were examined with participants' characteristics (i.e., age, gender and occupational category) using Fisher's exact test. Knowledge about periodontitis significantly improved immediately after receiving the health education, and this effect of education was evident one month later. However, not all of the knowledge was sufficiently retained one month after the education session. The proportion of participants undertaking desirable oral health actions

Structural and physico-chemical properties of insoluble rice bran fiber: effect of acid–base induced modifications

USDA-ARS?s Scientific Manuscript database

The structural modifications of insoluble rice bran fiber (IRBF) by sequential regimes of sulphuric acid (H2SO4) and their effects on the physicochemical attributes were studied. The increment of H2SO4 concentration resulted in decreased water holding capacity that ultimately enhanced the oil bindin...

Does attention redirection contribute to the effectiveness of attention bias modification on social anxiety?

PubMed

Yao, Nisha; Yu, Hongyu; Qian, Mingyi; Li, Songwei

2015-12-01

Attention bias modification (ABM) is designed to modify threat-related attention bias and thus alleviate anxiety. The current research examined whether consistently directing attention towards targeted goals per se contributes to ABM efficacy. We randomly assigned 68 non-clinical college students with elevated social anxiety to non-valence-specific attend-to-geometrics (AGC), attention modification (AMC), or attention control (ACC) conditions. We assessed subjective, behavioral, and physiological reactivity to a speech task and self-reported social anxiety symptoms. After training, participants in the AMC exhibited an attention avoidance from threat, and those in the AGC responded more rapidly toward targeted geometrics. There was a significant pre- to post-reduction in subjective speech distress across groups, but behavioral and physiological reactivity to speech, as well as self-report social anxiety symptoms, remained unchanged. These results lead to questions concerning effectiveness of ABM training for reducing social anxiety. Further examination of the current ABM protocol is required. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Inhibitive effect of matrine modification X on the growth of human nasopharyngeal carcinoma CNE2 cell xenografts in nude mice].

PubMed

Shi, Shujing; Tang, Anzhou; Yin, Shaolin; Wang, Lisheng; Xie, Mao; Yi, Xiang

2014-11-01

To evaluate the inhibitive effect of matrine modification X on the growth of human nasopharyngeal carcinoma CNE2 cell xenografts in nude mice. Tumor model was established by subcutaneous inoculation of nasopharyngeal carcinoma cell CNE2 into nude mice, which was used to evaluate the antitumor effect of matrine modification X in vivo. The expression levels of Bax, Bcl-2, Caspase3 were detected by real-time PCR and western blot. The growth of xenografts in nude mice was significantly suppressed after application of matrine modification X in a dose-dependent manner. The inhibition rates were 32.55% and 44.89% when treated at medium and high dose respectively. Real-time fluorescence quantitative-PCR and Western Blot results showed that the expression of Bax and Caspase3 increased, while the expression of Bcl-2 decreased in a dose-dependent manner. The change of high dose group was obvious, and the difference was statistically significant (P < 0.05). Matrine modification X could significantly inhibit the growth of human nasopharyngeal carcinoma CNE2 cell xenografts in nude mice, probably by inducing the apoptosis of nasopharyngeal carcinoma cells, and the possible mechanism is related to regulating the expression level of Bax/Bcl-2 and Casepase3.

Effects of energetic particle phase space modifications by instabilities on integrated modeling

NASA Astrophysics Data System (ADS)

Podestà, M.; Gorelenkova, M.; Fredrickson, E. D.; Gorelenkov, N. N.; White, R. B.

2016-11-01

Tokamak plasmas can feature a large population of energetic particles (EP) from neutral beam injection or fusion reactions. In turn, energetic particles can drive instabilities, which affect the driving EP population leading to a distortion of the original EP distribution function and of quantities that depend on it. The latter include, for example, neutral beam (NB) current drive and plasma heating through EP thermalization. Those effects must be taken into account to enable reliable and quantitative simulations of discharges for present devices as well as predictions for future burning plasmas. Reduced models for EP transport are emerging as an effective tool for long time-scale integrated simulations of tokamak plasmas, possibly including the effects of instabilities on EP dynamics. Available models differ in how EP distribution properties are modified by instabilities, e.g. in terms of gradients in real or phase space. It is therefore crucial to assess to what extent different assumptions in the transport models affect predicted quantities such as EP profile, energy distribution, NB driven current and energy/momentum transfer to the thermal populations. A newly developed kick model, which includes modifications of the EP distribution by instabilities in both real and velocity space, is used in this work to investigate these issues. Coupled to TRANSP simulations, the kick model is used to analyze NB-heated NSTX and DIII-D discharges featuring unstable Alfvén eigenmodes (AEs). Results show that instabilities can strongly affect the EP distribution function, and modifications propagate to macroscopic quantities such as NB-driven current profile and NB power transferred to the thermal plasma species. Those important aspects are only qualitatively captured by simpler fast ion transport models that are based on radial diffusion of energetic ions only.

Reported association of air pollution and suicide rate could be confounded.

PubMed

Afshari, R

2017-02-28

A statistical association between ambient air pollution and suicide mortality has been recently reported in Environmental Health, which seems not to be scientifically supported by their data.In this article, very low (unrealistic) suicide rate is reported, which is subjected to selection bias. Their justification is also flawed as high exposure to ambient air pollution in rural areas is lower as compared to urban residents. Weekends, holidays, time of death … are also both air pollution and suicide rate related. Reported statistical association of air pollution and suicide in this study is heavily confound.Please see article under discussion: https://ehjournal.biomedcentral.com/articles/10.1186/s12940-016-0177-1 .

Tungstate-induced color-pattern modifications of butterfly wings are independent of stress response and ecdysteroid effect.

PubMed

Otaki, Joji M; Ogasawara, Tsuyoshi; Yamamoto, Haruhiko

2005-06-01

Systemic injections of sodium tungstate, a protein-tyrosine phosphatase (PTPase) inhibitor, to pupae immediately after pupation have been shown to efficiently produce characteristic color-pattern modifications on the wings of many species of butterflies. Here we demonstrated that the tungstate-induced modification pattern was entirely different from other chemically-induced ones in a species of nymphalid butterfly Junonia (Precis) orithya. In this species, the systemic injections of tungstate produced characteristic expansion of black area and shrinkage of white area together with the move of parafocal elements toward the wing base. Overall, pattern boundaries became obscure. In contrast, an entirely different modification pattern, overall darkening of wings, was observed by the injections of stress-inducing chemicals, thapsigargin, ionomycin, or geldanamycin, to pupae under the rearing conditions for the adult summer form. On the ventral wings, this darkening was due to an increase of the proportion of peppered dark scales, which was reminiscent of the natural fall form of this species. Under the same rearing conditions, the injections of ecdysteroid, which is a well-known hormone being responsible for the seasonal polyphenism of nymphalid butterflies, yielded overall expansion of orange area especially around eyespots. Taken together, we conclude that the tungstate-induced modifications are clearly distinguishable from those of stress response and ecdysteroid effect. This conclusion then suggests that the putative PTPase signaling pathway that is sensitive to tungstate uniquely contributes to the wing-wide color-pattern development in butterflies.

Modifications of the PCPT method for HJB equations

NASA Astrophysics Data System (ADS)

Kossaczký, I.; Ehrhardt, M.; Günther, M.

2016-10-01

In this paper we will revisit the modification of the piecewise constant policy timestepping (PCPT) method for solving Hamilton-Jacobi-Bellman (HJB) equations. This modification is called piecewise predicted policy timestepping (PPPT) method and if properly used, it may be significantly faster. We will quickly recapitulate the algorithms of PCPT, PPPT methods and of the classical implicit method and apply them on a passport option pricing problem with non-standard payoff. We will present modifications needed to solve this problem effectively with the PPPT method and compare the performance with the PCPT method and the classical implicit method.

Sequence tagging reveals unexpected modifications in toxicoproteomics

PubMed Central

Dasari, Surendra; Chambers, Matthew C.; Codreanu, Simona G.; Liebler, Daniel C.; Collins, Ben C.; Pennington, Stephen R.; Gallagher, William M.; Tabb, David L.

2010-01-01

Toxicoproteomic samples are rich in posttranslational modifications (PTMs) of proteins. Identifying these modifications via standard database searching can incur significant performance penalties. Here we describe the latest developments in TagRecon, an algorithm that leverages inferred sequence tags to identify modified peptides in toxicoproteomic data sets. TagRecon identifies known modifications more effectively than the MyriMatch database search engine. TagRecon outperformed state of the art software in recognizing unanticipated modifications from LTQ, Orbitrap, and QTOF data sets. We developed user-friendly software for detecting persistent mass shifts from samples. We follow a three-step strategy for detecting unanticipated PTMs in samples. First, we identify the proteins present in the sample with a standard database search. Next, identified proteins are interrogated for unexpected PTMs with a sequence tag-based search. Finally, additional evidence is gathered for the detected mass shifts with a refinement search. Application of this technology on toxicoproteomic data sets revealed unintended cross-reactions between proteins and sample processing reagents. Twenty five proteins in rat liver showed signs of oxidative stress when exposed to potentially toxic drugs. These results demonstrate the value of mining toxicoproteomic data sets for modifications. PMID:21214251

Covariance between predation risk and nutritional preferences confound interpretations of giving-up density experiments.

PubMed

McMahon, Jordan D; Lashley, Marcus A; Brooks, Christopher P; Barton, Brandon T

2018-04-26

Giving-up density (GUD) experiments have been a foundational method to evaluate perceived predation risk, but rely on the assumption that food preferences are absolute, so that areas with higher GUDs can be interpreted as having higher risk. However, nutritional preferences are context dependent and can change with risk. We used spiders and grasshoppers to test the hypothesis that covariance in nutritional preferences and risk may confound the interpretation of GUD experiments. We presented grasshoppers with carbohydrate-rich and protein-rich diets, in the presence and absence of spider predators. Predators reduced grasshopper preference for the protein-rich food, but increased their preference for the carbohydrate-rich food. We then measured GUDs with both food types under different levels of risk (spider density, 0 - 5). As expected, GUDs increased with spider density indicating increasing risk, but only when using protein-rich food. With carbohydrate-rich food, GUD was independent of predation risk. Our results demonstrate that predation risk and nutritional preferences covary and can confound interpretation of GUD experiments. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Effects of oxidative modification on thermal aggregation and gel properties of soy protein by malondialdehyde.

PubMed

Wu, Wei; Hua, Yufei; Lin, Qinlu

2014-03-01

Malondialdehyde (MDA) was selected as a representative of lipid peroxidation products to investigate the effects of oxidative modification on thermal aggregation and gel properties of soy protein by lipid peroxidation products. Incubation of soy protein with increasing concentration of MDA resulted in gradual decrease of particle size and content of thermal aggregates during heat denaturation. Oxidative modification by MDA resulted in a decrease in water holding capacity, gel hardness, and gel strength of soy protein gel. An increase in coarseness and interstice of MDA modified protein gel network was accompanied by uneven distribution of interstice as MDA concentration increased. The results showed that degree of thermal aggregation of MDA-modified soy protein gradually decreased as MDA concentration increased, which contributed to a decrease in water holding capacity, gel hardness, and gel strength of MDA-modified soy protein gel.

The effects of lifestyle modification on symptoms and quality of life in patients with irritable bowel syndrome: a prospective observational study.

PubMed

Kang, Sun Hyung; Choi, Seong-Woo; Lee, Seung Jun; Chung, Woo Suk; Lee, Hye Ran; Chung, Ki-Young; Lee, Eaum Seok; Moon, Hee Seok; Kim, Seok Hyun; Sung, Jae Kyu; Lee, Byung Seok; Jeong, Hyun Yong

2011-12-01

Although notably common, irritable bowel syndrome (IBS) has no specific cure. Lifestyle modification may be as important as medication; however, few studies support the effectiveness of such modifications. We performed this observational study of IBS patients to explore further the role of lifestyle changes in treatment. This study included 831 men who enlisted in 2010 as armed surgeon cadets and 85 women who concurrently entered the Armed Forces Nursing Academy. Of these 916 participants, 89 were diagnosed with IBS using the Rome III criteria. Subjective changes in bowel habits, quality of life, pain, stress, stool frequency and stool consistency were surveyed before and after 9 weeks of army training. We evaluated the lifestyle risk factors that impacted improvement in IBS symptoms by comparing those who responded to lifestyle modification (the responding group) to those who did not respond (the nonresponding group). More than half of the participants (63%) reported that their symptoms improved after training. The quality of life and levels of pain and stress significantly improved after military training. Initial stress levels before military training and smoking history affected IBS symptom improvement. Lifestyle modification may be effective in managing IBS patients.

48 CFR 217.7103-6 - Modification of master agreements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Modification of master... Master Agreement for Repair and Alteration of Vessels 217.7103-6 Modification of master agreements. (a) Review each master agreement at least annually before the anniversary of its effective date and revise it...

48 CFR 217.7103-6 - Modification of master agreements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Modification of master... Master Agreement for Repair and Alteration of Vessels 217.7103-6 Modification of master agreements. (a) Review each master agreement at least annually before the anniversary of its effective date and revise it...

48 CFR 217.7103-6 - Modification of master agreements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Modification of master... Master Agreement for Repair and Alteration of Vessels 217.7103-6 Modification of master agreements. (a) Review each master agreement at least annually before the anniversary of its effective date and revise it...

48 CFR 217.7103-6 - Modification of master agreements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Modification of master... Master Agreement for Repair and Alteration of Vessels 217.7103-6 Modification of master agreements. (a) Review each master agreement at least annually before the anniversary of its effective date and revise it...

48 CFR 217.7103-6 - Modification of master agreements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Modification of master... Master Agreement for Repair and Alteration of Vessels 217.7103-6 Modification of master agreements. (a) Review each master agreement at least annually before the anniversary of its effective date and revise it...

Evaluation in medical education: A topical review of target parameters, data collection tools and confounding factors.

PubMed

Schiekirka, Sarah; Feufel, Markus A; Herrmann-Lingen, Christoph; Raupach, Tobias

2015-01-01

Evaluation is an integral part of education in German medical schools. According to the quality standards set by the German Society for Evaluation, evaluation tools must provide an accurate and fair appraisal of teaching quality. Thus, data collection tools must be highly reliable and valid. This review summarises the current literature on evaluation of medical education with regard to the possible dimensions of teaching quality, the psychometric properties of survey instruments and potential confounding factors. We searched Pubmed, PsycINFO and PSYNDEX for literature on evaluation in medical education and included studies published up until June 30, 2011 as well as articles identified in the "grey literature". RESULTS are presented as a narrative review. We identified four dimensions of teaching quality: structure, process, teacher characteristics, and outcome. Student ratings are predominantly used to address the first three dimensions, and a number of reliable tools are available for this purpose. However, potential confounders of student ratings pose a threat to the validity of these instruments. Outcome is usually operationalised in terms of student performance on examinations, but methodological problems may limit the usability of these data for evaluation purposes. In addition, not all examinations at German medical schools meet current quality standards. The choice of tools for evaluating medical education should be guided by the dimension that is targeted by the evaluation. Likewise, evaluation results can only be interpreted within the context of the construct addressed by the data collection tool that was used as well as its specific confounding factors.

Using the Modification Index and Standardized Expected Parameter Change for Model Modification

ERIC Educational Resources Information Center

Whittaker, Tiffany A.

2012-01-01

Model modification is oftentimes conducted after discovering a badly fitting structural equation model. During the modification process, the modification index (MI) and the standardized expected parameter change (SEPC) are 2 statistics that may be used to aid in the selection of parameters to add to a model to improve the fit. The purpose of this…

Crab shell chitin whiskers reinforced natural rubber nanocomposites. 3. Effect of chemical modification of chitin whiskers.

PubMed

Gopalan Nair, Kalaprasad; Dufresne, Alain; Gandini, Alessandro; Belgacem, Mohamed Naceur

2003-01-01

The purpose of this study was to chemically modify the surface of chitin whiskers and to investigate the effect of the incorporation of these modified whiskers into a natural rubber (NR) matrix on the properties of the ensuing nanocomposite. Different chemical coupling agents were tested, namely, phenyl isocyanate (PI), alkenyl succinic anhydride (ASA) (Accosize 18 from American Cyanamid), and 3-isopropenyl-alpha,alpha'-dimethylbenzyl isocyanate (TMI). The extent of chemical modification was evaluated by Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), and surface energy analysis. After chemical modification, nanocomposite films were obtained using a toluene natural rubber solution in which the whiskers were dispersed. Their mechanical properties were found to be inferior to those of unmodified chitin/NR composites presented in our previous study. In fact, even though there is an increase in filler-matrix interaction as a result of chemical modification of the chitin whiskers, this does not contribute to the improvement in the mechanical properties of the resulting nanocomposite. It is concluded that this loss of performance is due to the partial destruction of the three-dimensional network of chitin whiskers assumed to be present in the unmodified composites.

Starch--value addition by modification.

PubMed

Tharanathan, Rudrapatnam N

2005-01-01

Starch is one of the most important but flexible food ingredients possessing value added attributes for innumerable industrial applications. Its various chemically modified derivatives offer a great scope of high technological value in both food and non-food industries. Modified starches are designed to overcome one or more of the shortcomings, such as loss of viscosity and thickening power upon cooking and storage, particularly at low pH, retrogradation characteristics, syneresis, etc., of native starches. Oxidation, esterification, hydroxyalkylation, dextrinization, and cross-linking are some of the modifications commonly employed to prepare starch derivatives. In a way, starch modification provides desirable functional attributes as well as offering economic alternative to other hydrocolloid ingredients, such as gums and mucilages, which are unreliable in quality and availability. Resistant starch, a highly retrograded starch fractionformed upon food processing, is another useful starch derivative. It exhibits the beneficial physiological effects of therapeutic and nutritional values akin to dietary fiber. There awaits considerable opportunity for future developments, especially for tailor-made starch derivatives with multiple modifications and with the desired functional and nutritional properties, although the problem of obtaining legislative approval for the use of novel starch derivatives in processed food formulations is still under debate. Nevertheless, it can be predicted that new ventures in starch modifications and their diverse applications will continue to be of great interest in applied research.

Effect of conditions of modification on thermal and rheological properties of phosphorylated pumpkin starch.

PubMed

Przetaczek-Rożnowska, Izabela; Fortuna, Teresa

2017-11-01

This study aimed at analyzing the effect of conditions of modification process on thermal and rheological properties of phosphorylated pumpkin starch. The esterification process was conducted at 115°C and 145°C for 1, 2, and 3h. The thermodynamic properties of samples were determined using differential scanning calorimetry (DSC), flow curves were plotted and the resulting curves were described the Herschel-Bulkley model, textural properties were evaluated with the TPA method. The data proved that the chemical modification of starch affected its rheological and thermal characteristics, but the direction and extent of the changes were found to depend on both temperature and duration of phoshorylation. The results demonstrated that temperatures of gelatinization of the samples modified at 145°C were higher by 1.4-8.5°C than those of the samples obtained at 115°C. Prolongation of starch modification at 115°C caused reduction of shear stress (from 2.10Pa to 0.86Pa), and higher temperature of esterification also reduced the value of this parameter. The hardness of the samples heated at 145°C was higher by 45-59N than that of heated at 115°C. Adjustment of phosphorylation process caused an increase in gumminess by 1.8-37.9N, wherein higher temperature and process prolongation resulted in the highest gumminess. Copyright © 2017 Elsevier B.V. All rights reserved.

Salmonella enterica Serovar Typhi Lipopolysaccharide O-Antigen Modification Impact on Serum Resistance and Antibody Recognition

DOE PAGES

Kintz, Erica; Heiss, Christian; Black, Ian; ...

2017-02-06

Salmonella enterica serovar Typhi is a human-restricted Gram-negative bacterial pathogen responsible for causing an estimated 27 million cases of typhoid fever annually, leading to 217,000 deaths, and current vaccines do not offer full protection. The O-antigen side chain of the lipopolysaccharide is an immunodominant antigen, can define host-pathogen interactions, and is under consideration as a vaccine target for some Gram-negative species. The composition of the O-antigen can be modified by the activity of glycosyltransferase (gtr) operons acquired by horizontal gene transfer. Here we investigate the role of two gtr operons that we identified in the S. Typhi genome. Strains weremore » engineered to express specific gtr operons. Full chemical analysis of the O-antigens of these strains identified gtr-dependent glucosylation and acetylation. The glucosylated form of the O-antigen mediated enhanced survival in human serum and decreased complement binding. A single nucleotide deviation from an epigenetic phase variation signature sequence rendered the expression of this glucosylating gtr operon uniform in the population. In contrast, the expression of the acetylating gtrC gene is controlled by epigenetic phase variation. Acetylation did not affect serum survival, but phase variation can be an immune evasion mechanism, and thus, this modification may contribute to persistence in a host. In murine immunization studies, both O-antigen modifications were generally immunodominant. Our results emphasize that natural O-antigen modifications should be taken into consideration when assessing responses to vaccines, especially O-antigen-based vaccines, and that the Salmonella gtr repertoire may confound the protective efficacy of broad-ranging Salmonella lipopolysaccharide conjugate vaccines.« less

Salmonella enterica Serovar Typhi Lipopolysaccharide O-Antigen Modification Impact on Serum Resistance and Antibody Recognition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kintz, Erica; Heiss, Christian; Black, Ian

Salmonella enterica serovar Typhi is a human-restricted Gram-negative bacterial pathogen responsible for causing an estimated 27 million cases of typhoid fever annually, leading to 217,000 deaths, and current vaccines do not offer full protection. The O-antigen side chain of the lipopolysaccharide is an immunodominant antigen, can define host-pathogen interactions, and is under consideration as a vaccine target for some Gram-negative species. The composition of the O-antigen can be modified by the activity of glycosyltransferase (gtr) operons acquired by horizontal gene transfer. Here we investigate the role of two gtr operons that we identified in the S. Typhi genome. Strains weremore » engineered to express specific gtr operons. Full chemical analysis of the O-antigens of these strains identified gtr-dependent glucosylation and acetylation. The glucosylated form of the O-antigen mediated enhanced survival in human serum and decreased complement binding. A single nucleotide deviation from an epigenetic phase variation signature sequence rendered the expression of this glucosylating gtr operon uniform in the population. In contrast, the expression of the acetylating gtrC gene is controlled by epigenetic phase variation. Acetylation did not affect serum survival, but phase variation can be an immune evasion mechanism, and thus, this modification may contribute to persistence in a host. In murine immunization studies, both O-antigen modifications were generally immunodominant. Our results emphasize that natural O-antigen modifications should be taken into consideration when assessing responses to vaccines, especially O-antigen-based vaccines, and that the Salmonella gtr repertoire may confound the protective efficacy of broad-ranging Salmonella lipopolysaccharide conjugate vaccines.« less

Lifestyle modification in the management of the metabolic syndrome: achievements and challenges

PubMed Central

Grave, Riccardo Dalle; Calugi, Simona; Centis, Elena; Marzocchi, Rebecca; Ghoch, Marwan El; Marchesini, Giulio

2010-01-01

Lifestyle modification based on behavior therapy is the most important and effective strategy to manage the metabolic syndrome. Modern lifestyle modification therapy combines specific recommendations on diet and exercise with behavioral and cognitive strategies. The intervention may be delivered face-to-face or in groups, or in groups combined with individual sessions. The main challenge of treatment is helping patients maintain healthy behavior changes in the long term. In the last few years, several strategies have been evaluated to improve the long-term effect of lifestyle modification. Promising results have been achieved by combining lifestyle modification with pharmacotherapy, using meals replacement, setting higher physical activity goals, and long-term care. The key role of cognitive processes in the success/failure of weight loss and maintenance suggests that new cognitive procedures and strategies should be included in the traditional lifestyle modification interventions, in order to help patients build a mind-set favoring long-term lifestyle changes. These new strategies raise optimistic expectations for an effective treatment of metabolic syndrome with lifestyle modifications, provided public health programs to change the environment where patients live support them. PMID:21437107

Effects of compositional modifications on the sensitization behavior of FeCrMn steels

NASA Astrophysics Data System (ADS)

Edgemon, G. L.; Tortorelli, P. F.; Bell, G. E. C.

1992-09-01

FeCrMn may possibly be used in conjunction with aqueous blankets or cooants in a fusion device. Therefore, standard chemical immersion (modified Strauss) tests were conducted to characterize the effects of compositional modifications on the thermal sensitization behavior of these steels. A good correlation among weight losses, intergranular corrosion, and cracking was found. The most effective means of decreasing their susceptibility was through reduction of the carbon concentration of these steels to 0.1%, but the sensitization resistance of FeCrMn0.1 C compositions was still inferior to type 304L and other similar stainless steels. Alloying additions that form stable carbides did not have a very significant influence on the sensitization behavior.

Residential Modifications and Decline in Physical Function among Community-Dwelling Older Adults

ERIC Educational Resources Information Center

Liu, Sze Y.; Lapane, Kate L.

2009-01-01

Purpose: The purpose of this study is to quantify the effect of residential modification on decreasing risk of physical function decline in 2 years. Design: Cohort study using propensity scores method to control for baseline differences between individuals with residential modifications and those without residential modifications. Participants:…

Confounding of the association between statins and Parkinson disease: systematic review and meta-analysis.

PubMed

Bykov, Katsiaryna; Yoshida, Kazuki; Weisskopf, Marc G; Gagne, Joshua J

2017-03-01

Both statins and higher serum cholesterol have been reported to reduce to risk of Parkinson Disease (PD). Given the importance of adjusting for cholesterol levels when evaluating the effect of statins, we assessed whether the protective effect of statins would remain when adjustment for cholesterol is performed. We conducted a systematic review of epidemiologic studies that reported quantitative estimates of the association between statins and incident PD and were published through February 2016. Random-effects meta-analysis was used to assess the effect of statins on PD separately among the studies that adjusted for either cholesterol or hyperlipidemia and studies that did not. Ten eligible studies that evaluated the use of statins and incident PD were identified. Among the six studies that did not adjust for cholesterol, a protective effect of statins was observed (relative risk 0.75; 95% confidence intervals (CI) 0.60 to 0.92). Excluding studies with possible bias because of reverse causation or stratifying on study design did not affect the results. No protective effect was observed among the four studies that adjusted for either cholesterol of hyperlipidemia (relative risk 0.91; 95%CI 0.68 to 1.22). The effect estimate for studies that adjusted for cholesterol was 1.04 (95%CI 0.68 to 1.59) when a study with immortal time bias was excluded. The apparent protective effect of statins on risk of PD is at least partially explained by confounding by statin indication. Immortal time bias and healthy user effects also could have contributed to biased results. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Controlling for confounding variables in MS-omics protocol: why modularity matters.

PubMed

Smith, Rob; Ventura, Dan; Prince, John T

2014-09-01

As the field of bioinformatics research continues to grow, more and more novel techniques are proposed to meet new challenges and improvements upon solutions to long-standing problems. These include data processing techniques and wet lab protocol techniques. Although the literature is consistently thorough in experimental detail and variable-controlling rigor for wet lab protocol techniques, bioinformatics techniques tend to be less described and less controlled. As the validation or rejection of hypotheses rests on the experiment's ability to isolate and measure a variable of interest, we urge the importance of reducing confounding variables in bioinformatics techniques during mass spectrometry experimentation. © The Author 2013. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Effects of channel modifications on the hydrology of Chicod Creek basin, North Carolina, 1975-87

USGS Publications Warehouse

Mason, R.R.; Simmons, C.E.; Watkins, S.A.

1990-01-01

Drainage modifications in this Coastal Plain basin from 1978 to 1981 consisted of channel excavation and clearing of blockages. A study was begun in 1975 to define hydrologic conditions of the basin before, during, and after modifications and to determine what changes were attributed to modifications. Surface-water conditions were altered during and following modifications. Minimum flow at Juniper Branch was increased from less than 0.1 cu ft/sec to 0.4 cu ft/second;streamflow variability was reduced from an index of 0.87 to 0.49. In-channel velocity at Chicod Creek was increased from a mean of 0.4 ft/sec to 1.5 ft/sec. Substantial groundwater level declines were observed in wells 180 and 250 ft from Juniper Branch during the modifications phase;these were 0.4 and 0.2 ft, respectively. However, most surface-water and groundwater conditions returned nearly to premodification levels by 1987. Water-quality characteristics monitored during the investigation included physical, chemical, and bacteriological characteristics. Physical characteristics monitored were suspended sediment, temperature, dissolved oxygen, and pH. Of these physical characteristics, only sediment concentrations increased substantially during channel modifications. Chemical characteristics studied were major dissolved constituents, nutrients, trace metals, and pesticides. Substantial changes ranged from a decline in total iron concentrations of 77% to an increase in total nitrite concentrations of 130%. Changes in many chemical characteristics persisted following channel modifications. Bacterial counts did not change substantially.

Surface Modification of Intraocular Lenses

PubMed Central

Huang, Qi; Cheng, George Pak-Man; Chiu, Kin; Wang, Gui-Qin

2016-01-01

Objective: This paper aimed to review the current literature on the surface modification of intraocular lenses (IOLs). Data Sources: All articles about surface modification of IOLs published up to 2015 were identified through a literature search on both PubMed and ScienceDirect. Study Selection: The articles on the surface modification of IOLs were included, but those on design modification and surface coating were excluded. Results: Technology of surface modification included plasma, ion beam, layer-by-layer self-assembly, ultraviolet radiation, and ozone. The main molecules introduced into IOLs surface were poly (ethylene glycol), polyhedral oligomeric silsesquioxane, 2-methacryloyloxyethyl phosphorylcholine, TiO2, heparin, F-heparin, titanium, titanium nitride, vinyl pyrrolidone, and inhibitors of cytokines. The surface modification either resulted in a more hydrophobic lens, a more hydrophilic lens, or a lens with a hydrophilic anterior and hydrophobic posterior surface. Advances in research regarding surface modification of IOLs had led to a better biocompatibility in both in vitro and animal experiments. Conclusion: The surface modification is an efficient, convenient, economic and promising method to improve the biocompatibility of IOLs. PMID:26830993

Status of lifestyle modifications in hypertension.

PubMed

Chhabra, M K; Lal, A; Sharma, K K

2001-09-01

Hypertension is essentially the elevation of arterial blood pressure beyond an arbitrary cut off point, though the dividing line between normal and elevated BP is lacking. Hypertension can be classified into primary, essential or idiopathic hypertension on one hand, and secondary one due to some disease itself. In treating hypertension, antihypertensives have their role, but attention may be directed towards some lifestyle modifications. As regarding dietary interventions, calorie restriction may influence the minimisation of BP. Body weight reduction, less alcohol consumption, salt restriction, potassium and calcium supplementation can enhance the process of lowering BP. The role of magnesium in hypertension is debatable. Serum cholesterol level is commonly elevated in hypertensive patients and its reduction reduces the risk of non-fatal coronary events. Diet rich in plant fibres either alone or with a low fat, low sodium could lower the BP by about 5 mm Hg in hypertensives. The omega-3-polyunsaturated fatty acids found in highest concentrations in cold water fishes have a modest antihypertensive effect. Caffeine contained in two cups of coffee may raise the BP by 5 mm Hg in infrequent users but in habitual users, caffeine has no role. Deficiency of vitamin C might lead to hypertension. As regarding behavioural changes, stopping smoking, regular physical exercise, relaxation therapies like yoga, etc, have definite beneficial effect on hypertensives. The antihypertensive effect of lifestyle modifications may obviate drug therapy. For this one or more of the lifestyle modifications should be tried initially in all hypertensive patients.

Meta-analysis of the effects of academic interventions and modifications on student behavior outcomes.

PubMed

Warmbold-Brann, Kristy; Burns, Matthew K; Preast, June L; Taylor, Crystal N; Aguilar, Lisa N

2017-09-01

The current study examined the effect of academic interventions and modifications on behavioral outcomes in a meta-analysis of 32 single-case design studies. Academic interventions included modifying task difficulty, providing instruction in reading, mathematics, or writing, and contingent reinforcement for academic performance. There was an overall small to moderate effect (ϕ = .56) on behavioral outcomes, with a stronger effect on increasing time on task (ϕ = .64) than on decreasing disruptive behavior (ϕ = .42). There was a small effect for using a performance-based contingent reinforcer (ϕ = .48). Interventions completed in an individual setting resulted in a moderate to large effects on behavior outcomes. Results of the current meta-analysis suggest that academic interventions can offer both positive academic and behavioral outcomes. Practical implications and suggestions for future research are included. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Proteomic Investigation of Protein Profile Changes and Amino Acid Residue Level Modification in Cooked Lamb Meat: The Effect of Boiling.

PubMed

Yu, Tzer-Yang; Morton, James D; Clerens, Stefan; Dyer, Jolon M

2015-10-21

Hydrothermal treatment (heating in water) is a common method of general food processing and preparation. For red-meat-based foods, boiling is common; however, how the molecular level effects of this treatment correlate to the overall food properties is not yet well-understood. The effects of differing boiling times on lamb meat and the resultant cooking water were here examined through proteomic evaluation. The longer boiling time was found to result in increased protein aggregation involving particularly proteins such as glyceraldehyde-3-phosphate dehydrogenase, as well as truncation in proteins such as in α-actinin-2. Heat-induced protein backbone cleavage was observed adjacent to aspartic acid and asparagine residues. Side-chain modifications of amino acid residues resulting from the heating, including oxidation of phenylalanine and formation of carboxyethyllysine, were characterized in the cooked samples. Actin and myoglobin bands from the cooked meat per se remained visible on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, even after significant cooking time. These proteins were also found to be the major source of observed heat-induced modifications. This study provides new insights into molecular-level modifications occurring in lamb meat proteins during boiling and a protein chemistry basis for better understanding the effect of this common treatment on the nutritional and functional properties of red-meat-based foods.

Combined Pulmonary Fibrosis and Emphysema in Scleroderma-Related Lung Disease Has a Major Confounding Effect on Lung Physiology and Screening for Pulmonary Hypertension.

PubMed

Antoniou, K M; Margaritopoulos, G A; Goh, N S; Karagiannis, K; Desai, S R; Nicholson, A G; Siafakas, N M; Coghlan, J G; Denton, C P; Hansell, D M; Wells, A U

2016-04-01

To assess the prevalence of combined pulmonary fibrosis and emphysema (CPFE) in systemic sclerosis (SSc) patients with interstitial lung disease (ILD) and the effect of CPFE on the pulmonary function tests used to evaluate the severity of SSc-related ILD and the likelihood of pulmonary hypertension (PH). High-resolution computed tomography (HRCT) scans were obtained in 333 patients with SSc-related ILD and were evaluated for the presence of emphysema and the extent of ILD. The effects of emphysema on the associations between pulmonary function variables and the extent of SSc-related ILD as visualized on HRCT and echocardiographic evidence of PH were quantified. Emphysema was present in 41 (12.3%) of the 333 patients with SSc-related ILD, in 26 (19.7%) of 132 smokers, and in 15 (7.5%) of 201 lifelong nonsmokers. When the extent of fibrosis was taken into account, emphysema was associated with significant additional differences from the expected values for diffusing capacity for carbon monoxide (DLco) (average reduction of 24.1%; P < 0.0005), and the forced vital capacity (FVC)/DLco ratio (average increase of 34.8%; P < 0.0005) but not FVC. These effects were identical in smokers and nonsmokers. Multivariate analysis showed that the presence of emphysema had a greater effect than echocardiographically determined PH on the FVC/DLco ratio, regardless of whether it was analyzed as a continuous variable or using a threshold value of 1.6 or 2.0. Among patients with SSc-related ILD, emphysema is sporadically present in nonsmokers and is associated with a low pack-year history in smokers. The confounding effect of CPFE on measures of gas exchange has major implications for the construction of screening algorithms for PH in patients with SSc-related ILD. © 2016, American College of Rheumatology.

Effects of Low-Level Laser Therapy on M1-Related Cytokine Expression in Monocytes via Histone Modification

PubMed Central

Chen, Chia-Hsin; Wang, Chau-Zen; Wang, Yan-Hsiung; Liao, Wei-Ting; Chen, Yi-Jen; Kuo, Hsuan-Fu; Hung, Chih-Hsing

2014-01-01

Low-level laser therapy (LLLT) has been used in the treatment of radiotherapy-induced oral mucositis and allergic rhinitis. However, the effects of LLLT on human monocyte polarization into M1 macrophages are unknown. To evaluate the effects of LLLT on M1-related cytokine and chemokine production and elucidate the mechanism, the human monocyte cell line THP-1 was treated with different doses of LLLT. The expression of M1-related cytokines and chemokines (CCL2, CXCL10, and TNF-α) was determined by ELISA and real-time PCR. LLLT-associated histone modifications were examined by chromatin immunoprecipitation (ChIP) assays. Mitochondrial involvement in the LLLT-induced M1-related cytokine expression was evaluated by quantitative real-time PCR. Flow cytometry was used to detect the cell surface markers for monocyte polarization. The results showed that LLLT (660 nm) significantly enhanced M1-related cytokine and chemokine expression in mRNA and protein levels. Mitochondrial copy number and mRNA levels of complex I-V protein were increased by LLLT (1 J/cm2). Activation of M1 polarization was concomitant with histone modification at TNF-α gene locus and IP-10 gene promoter area. This study indicates that LLLT (660 nm) enhanced M1-related cytokine and chemokine expression via mitochondrial biogenesis and histone modification, which may be a potent immune-enhancing agent for the treatment of allergic diseases. PMID:24692853

Cryptic confounding compounds: A brief consideration of the influences of anthropogenic contaminants on courtship and mating behavior

PubMed Central

Blocker, Tomica D.; Ophir, Alexander G.

2012-01-01

Contaminants, like pesticides, polychlorinated biphenyls (PCBs), dioxins and metals, are persistent and ubiquitous and are known to threaten the environment. Traditionally, scientists have considered the direct physiological risks that these contaminants pose. However, scientists have just begun to integrate ethology and toxicology to investigate the effects that contaminants have on behavior. This review considers the potential for contaminant effects on mating behavior. Here we assess the growing body of research concerning disruptions in sexual differentiation, courtship, sexual receptivity, arousal, and mating. We discuss the implications of these disruptions on conservation efforts and highlight the importance of recognizing the potential for environmental stressors to affect behavioral experimentation. More specifically, we consider the negative implications for anthropogenic contaminants to affect the immediate behavior of animals, and their potential to have cascading and/or long-term effects on the behavioral ecology and evolution of populations. Overall, we aim to raise awareness of the confounding influence that contaminants can have, and promote caution when interpreting results where the potential for cryptic affects are possible. PMID:24244068

Early Exposure to Traffic-Related Air Pollution, Respiratory Symptoms at 4 Years of Age, and Potential Effect Modification by Parental Allergy, Stressful Family Events, and Sex: A Prospective Follow-up Study of the PARIS Birth Cohort

PubMed Central

Rancière, Fanny; Bougas, Nicolas; Viola, Malika; Momas, Isabelle

2016-01-01

Background: The relation between traffic-related air pollution (TRAP) exposure and the incidence of asthma/allergy in preschool children has been widely studied, but results remain heterogeneous, possibly due to differences in methodology and susceptibility to TRAP. Objectives: We aimed to study the relation of early TRAP exposure with the development of respiratory/allergic symptoms and asthma during preschool years, and to investigate parental allergy, “stressful” family events, and sex as possible effect modifiers. Methods: We examined data of 2,015 children from the PARIS birth cohort followed up with repeated questionnaires completed by parents until age 4 years. TRAP exposure in each child’s first year of life was estimated by nitrogen oxides (NOx) air dispersion modeling, taking into account both home and day care locations. Association between TRAP exposure and patterns of wheezing, dry night cough, and rhinitis symptoms was studied using multinomial logistic regression models adjusted for potential confounders. Effect modification by parental history of allergy, stressful family events, and sex was investigated. Results: An interquartile range (26 μg/m3) increase in NOx levels was associated with an increased odds ratio (OR) of persistent wheezing at 4 years (adjusted OR = 1.27; 95% confidence interval: 1.09, 1.47). TRAP exposure was positively associated with persistent wheeze, dry cough, and rhinitis symptoms among children with a parental allergy, those experiencing stressful family events, and boys, but not in children whose parents did not have allergies or experience stressful events, or in girls (all interaction p-values < 0.2). Conclusions: This study supports the hypothesis that not all preschool children are equal regarding TRAP health effects. Parental history of allergy, stressful family events, and male sex may increase their susceptibility to adverse respiratory effects of early TRAP exposure. Citation: Rancière F, Bougas N, Viola M

Base modification strategies to modulate immune stimulation by an siRNA.

PubMed

Valenzuela, Rachel Anne P; Suter, Scott R; Ball-Jones, Alexi A; Ibarra-Soza, José M; Zheng, Yuxuan; Beal, Peter A

2015-01-19

Immune stimulation triggered by siRNAs is one of the major challenges in the development of safe RNAi-based therapeutics. Within an immunostimulatory siRNA sequence, this hurdle is commonly addressed by using ribose modifications (e.g., 2'-OMe or 2'-F), which results in decreased cytokine production. However, as immune stimulation by siRNAs is a sequence-dependent phenomenon, recognition of the nucleobases by the trigger receptor(s) is also likely. Here, we use the recently published crystal structures of Toll-like receptor 8 (TLR8) bound to small-molecule agonists to generate computational models for ribonucleotide binding by this immune receptor. Our modeling suggested that modification of either the Watson-Crick or Hoogsteen face of adenosine would disrupt nucleotide/TLR8 interactions. We employed chemical synthesis to alter either the Watson-Crick or Hoogsteen face of adenosine and evaluated the effect of these modifications in an siRNA guide strand by measuring the immunostimulatory and RNA interference properties. For the siRNA guide strand tested, we found that modifying the Watson-Crick face is generally more effective at blocking TNFα production in human peripheral blood mononuclear cells (PBMCs) than modification at the Hoogsteen edge. We also observed that modifications near the 5'-end were more effective at blocking cytokine production than those placed at the 3'-end. This work advances our understanding of how chemical modifications can be used to optimize siRNA performance. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Research of Influence Modification of Natural Concentrate on Quality Metal

NASA Astrophysics Data System (ADS)

Fedoseev, S. N.; Gizatulin, R. A.; Korotkova, E. A.

2016-08-01

Questions of increase of mechanical, technological and service properties of metal at minimum cost to produce it are relevant for the metallurgical enterprises. Modification of complex steel alloys containing reactive elements is one of the effective ways to improve the quality of steel. At the same time the direct costs for the use of modifiers are 0.2-0.3%, which little effect on the cost of production. The paper presents the results of the application of natural concentrates as a modifier steel. The effects on the metal quality changes due to the impact of the modification concentrates demonstrate the effectiveness of their application. As a result of modification decreased the content of nonmetallic inclusions and grain size. Reduction of impurity modified metal of was the cause more high plastic properties, especially, impact strength at ordinary and low temperatures of tests. Based on the experimental data evaluated hardening mechanisms that lead to a significant improvement of physic-mechanical properties of the metal workpiece after administration modifier.

Cysteine Oxidative Post-translational Modifications: Emerging Regulation in the Cardiovascular System

PubMed Central

Chung, Heaseung S.; Wang, Sheng-Bing; Venkatraman, Vidya; Murray, Christopher I.; Van Eyk, Jennifer E.

2014-01-01

In the cardiovascular system, changes in the oxidative balance can affect many aspects of cellular physiology through redox-signaling. Depending on the magnitude, fluctuations in the cell's production of reactive oxygen and nitrogen species can regulate normal metabolic processes, activate protective mechanisms, or be cytotoxic. Reactive oxygen and nitrogen species can have many effects including the post-translational modification of proteins at critical cysteine (Cys) thiols. A subset can act as redox-switches, which elicit functional effects in response to changes in oxidative state. While the general concepts of redox-signaling have been established, the identity and function of many regulatory switches remains unclear. Characterizing the effects of individual modifications is the key to understanding how the cell interprets oxidative signals under physiological and pathological conditions. Here, we review the various Cys oxidative post-translational modifications (Ox-PTMs) and their ability to function as redox-switches that regulate the cell's response to oxidative stimuli. In addition, we discuss how these modifications have the potential to influence other post-translational modifications' signaling pathways though cross-talk. Finally, we review the growing number of tools being developed to identify and quantify the various Cys Ox-PTMs and how this will advance our understanding of redox-regulation. PMID:23329793

Evaluation of soil modification mixing procedures

DOT National Transportation Integrated Search

2001-01-01

Lime is routinely used as a soil modification agent in Kansas to improve the performance of subgrade soils with the primary goal of reducing volume change. Effective mixing of lime and soil is critical to ensuring that the expected improvements occur...

Exploratory study of the effects of wing-leading-edge modifications on the stall/spin behavior of a light general aviation airplane

NASA Technical Reports Server (NTRS)

1979-01-01

Configurations with full-span and segmented leading-edge flaps and full-span and segmented leading-edge droop were tested. Studies were conducted with wind-tunnel models, with an outdoor radio-controlled model, and with a full-scale airplane. Results show that wing-leading-edge modifications can produce large effects on stall/spin characteristics, particularly on spin resistance. One outboard wing-leading-edge modification tested significantly improved lateral stability at stall, spin resistance, and developed spin characteristics.

Effect of Autoclaved Aerated Concrete Modification with High-Impact Polystyrene on Sound Insulation

NASA Astrophysics Data System (ADS)

Brelak, Sylwia; Dachowski, Ryszard

2017-10-01

Autoclaved aerated concrete is one of the most commonly used building materials. Its advantages include low density, high thermal insulation capacity and high fire resistance. It has a relatively high compressive strength, though not high enough to be able to compete with other building materials in this respect. One of the directions leading to the improvement of physical and mechanical properties of autoclaved aerated concrete is the modification of its composition. A noticeable effect of pulverized high-impact polystyrene (improved compressive strength and water absorption) was relevant for the decision to continue the study of its effects. This paper discusses the effect of high-impact polystyrene on sound insulation in AAC products. The tests demonstrated a positive influence of the modifier on AAC sound insulation enhancement. Results from the tests performed on HIPS-modified AAC products were showed and compared with the properties of conventional products. The effect of the polymer on the microstructure of the products obtained was described briefly.

The Sander parallelogram illusion dissociates action and perception despite control for the litany of past confounds.

PubMed

Whitwell, Robert L; Goodale, Melvyn A; Merritt, Kate E; Enns, James T

2018-01-01

The two visual systems hypothesis proposes that human vision is supported by an occipito-temporal network for the conscious visual perception of the world and a fronto-parietal network for visually-guided, object-directed actions. Two specific claims about the fronto-parietal network's role in sensorimotor control have generated much data and controversy: (1) the network relies primarily on the absolute metrics of target objects, which it rapidly transforms into effector-specific frames of reference to guide the fingers, hands, and limbs, and (2) the network is largely unaffected by scene-based information extracted by the occipito-temporal network for those same targets. These two claims lead to the counter-intuitive prediction that in-flight anticipatory configuration of the fingers during object-directed grasping will resist the influence of pictorial illusions. The research confirming this prediction has been criticized for confounding the difference between grasping and explicit estimates of object size with differences in attention, sensory feedback, obstacle avoidance, metric sensitivity, and priming. Here, we address and eliminate each of these confounds. We asked participants to reach out and pick up 3D target bars resting on a picture of the Sander Parallelogram illusion and to make explicit estimates of the length of those bars. Participants performed their grasps without visual feedback, and were permitted to grasp the targets after making their size-estimates to afford them an opportunity to reduce illusory error with haptic feedback. The results show unequivocally that the effect of the illusion is stronger on perceptual judgments than on grasping. Our findings from the normally-sighted population provide strong support for the proposal that human vision is comprised of functionally and anatomically dissociable systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of energetic particle phase space modifications by instabilities on integrated modeling

DOE PAGES

Podesta, M.; Gorelenkova, M.; Fredrickson, E. D.; ...

2016-07-22

Tokamak plasmas can feature a large population of energetic particles (EP) from neutral beam injection or fusion reactions. In turn, energetic particles can drive instabilities, which affect the driving EP population leading to a distortion of the original EP distribution function and of quantities that depend on it. The latter include, for example, neutral beam (NB) current drive and plasma heating through EP thermalization. Those effects must be taken into account to enable reliable and quantitative simulations of discharges for present devices as well as predictions for future burning plasmas. Reduced models for EP transport are emerging as an effectivemore » tool for long time-scale integrated simulations of tokamak plasmas, possibly including the effects of instabilities on EP dynamics. Available models differ in how EP distribution properties are modified by instabilities, e.g. in terms of gradients in real or phase space. It is therefore crucial to assess to what extent different assumptions in the transport models affect predicted quantities such as EP profile, energy distribution, NB driven current and energy/momentum transfer to the thermal populations. A newly developed kick model, which includes modifications of the EP distribution by instabilities in both real and velocity space, is used in this work to investigate these issues. Coupled to TRANSP simulations, the kick model is used to analyze NB-heated NSTX and DIII-D discharges featuring unstable Alfvén eigenmodes (AEs). Results show that instabilities can strongly affect the EP distribution function, and modifications propagate to macroscopic quantities such as NB-driven current profile and NB power transferred to the thermal plasma species. Furthermore, those important aspects are only qualitatively captured by simpler fast ion transport models that are based on radial diffusion of energetic ions only.« less

Inverse probability weighting to control confounding in an illness-death model for interval-censored data.

PubMed

Gillaizeau, Florence; Sénage, Thomas; Le Borgne, Florent; Le Tourneau, Thierry; Roussel, Jean-Christian; Leffondrè, Karen; Porcher, Raphaël; Giraudeau, Bruno; Dantan, Etienne; Foucher, Yohann

2018-04-15

Multistate models with interval-censored data, such as the illness-death model, are still not used to any considerable extent in medical research regardless of the significant literature demonstrating their advantages compared to usual survival models. Possible explanations are their uncommon availability in classical statistical software or, when they are available, by the limitations related to multivariable modelling to take confounding into consideration. In this paper, we propose a strategy based on propensity scores that allows population causal effects to be estimated: the inverse probability weighting in the illness semi-Markov model with interval-censored data. Using simulated data, we validated the performances of the proposed approach. We also illustrated the usefulness of the method by an application aiming to evaluate the relationship between the inadequate size of an aortic bioprosthesis and its degeneration or/and patient death. We have updated the R package multistate to facilitate the future use of this method. Copyright © 2017 John Wiley & Sons, Ltd.

Study of the modifications needed for effective operation NASTRAN on IBM virtual storage computers

NASA Technical Reports Server (NTRS)

Mccormick, C. W.; Render, K. H.

1975-01-01

The necessary modifications were determined to make NASTRAN operational under virtual storage operating systems (VS1 and VS2). Suggested changes are presented which will make NASTRAN operate more efficiently under these systems. Estimates of the cost and time involved in design, coding, and implementation of all suggested modifications are included.

Public perceptions of hurricane modification.

PubMed

Klima, Kelly; Bruine de Bruin, Wändi; Morgan, M Granger; Grossmann, Iris

2012-07-01

If hurricane modification were to become a feasible strategy for potentially reducing hurricane damages, it would likely generate public discourse about whether to support its implementation. To facilitate an informed and constructive discourse, policymakers need to understand how people perceive hurricane modification. Here, we examine Florida residents' perceptions of hurricane modification techniques that aim to alter path and wind speed. Following the mental models approach, we conducted a survey study about public perceptions of hurricane modification that was guided by formative interviews on the topic. We report a set of four primary findings. First, hurricane modification was perceived as a relatively ineffective strategy for damage reduction, compared to other strategies for damage reduction. Second, hurricane modification was expected to lead to changes in projected hurricane path, but not necessarily to the successful reduction of projected hurricane strength. Third, more anger was evoked when a hurricane was described as having changed from the initially forecasted path or strength after an attempted modification. Fourth, unlike what we expected, participants who more strongly agreed with statements that recognized the uncertainty inherent in forecasts reported more rather than less anger at scientists across hurricane modification scenarios. If the efficacy of intensity-reduction techniques can be increased, people may be willing to support hurricane modification. However, such an effort would need to be combined with open and honest communications to members of the general public. © 2011 Society for Risk Analysis.

Does environmental confounding mask pleiotropic effects of a multiple sclerosis susceptibility variant on vitamin D in psychosis?

PubMed

Iyegbe, Conrad O; Acharya, Anita; Lally, John; Gardner-Sood, Poonam; Smith, Louise S; Smith, Shubulade; Murray, Robin; Howes, Oliver; Gaughran, Fiona

2015-01-01

This work addresses the existing and emerging evidence of overlap within the environmental and genetic profiles of multiple sclerosis (MS) and schizophrenia. To investigate whether a genetic risk factor for MS (rs703842), whose variation is indicative of vitamin D status in the disorder, could also be a determinant of vitamin D status in chronic psychosis patients. A cohort of 224 chronic psychosis cases was phenotyped and biologically profiled. The relationship between rs703842 and physiological vitamin D status in the blood plasma was assessed by logistic regression. Deficiency was defined as a blood plasma concentration below 10 ng/µl. Potential environmental confounders of the vitamin D status were considered as part of the analysis. We report suggestive evidence of an association with vitamin D status in established psychosis (ß standardized=0.51, P=0.04). The logistic model fit significantly benefited from controlling for body mass index, depression and ethnicity (χ (2)=91.7; 2 degrees of freedom (df); P=1.2×10(20)). The results suggest that, in addition to lifestyle changes that accompany the onset of illness, vitamin D dysregulation in psychosis has a genetic component that links into MS. Further, comprehensive studies are needed to evaluate this prospect.

Visual Search with Image Modification in Age-Related Macular Degeneration

PubMed Central

Wiecek, Emily; Jackson, Mary Lou; Dakin, Steven C.; Bex, Peter

2012-01-01

Purpose. AMD results in loss of central vision and a dependence on low-resolution peripheral vision. While many image enhancement techniques have been proposed, there is a lack of quantitative comparison of the effectiveness of enhancement. We developed a natural visual search task that uses patients' eye movements as a quantitative and functional measure of the efficacy of image modification. Methods. Eye movements of 17 patients (mean age = 77 years) with AMD were recorded while they searched for target objects in natural images. Eight different image modification methods were implemented and included manipulations of local image or edge contrast, color, and crowding. In a subsequent task, patients ranked their preference of the image modifications. Results. Within individual participants, there was no significant difference in search duration or accuracy across eight different image manipulations. When data were collapsed across all image modifications, a multivariate model identified six significant predictors for normalized search duration including scotoma size and acuity, as well as interactions among scotoma size, age, acuity, and contrast (P < 0.05). Additionally, an analysis of image statistics showed no correlation with search performance across all image modifications. Rank ordering of enhancement methods based on participants' preference revealed a trend that participants preferred the least modified images (P < 0.05). Conclusions. There was no quantitative effect of image modification on search performance. A better understanding of low- and high-level components of visual search in natural scenes is necessary to improve future attempts at image enhancement for low vision patients. Different search tasks may require alternative image modifications to improve patient functioning and performance. PMID:22930725

Genetic modifications for personal enhancement: a defence.

PubMed

Murphy, Timothy F

2014-04-01

Bioconservative commentators argue that parents should not take steps to modify the genetics of their children even in the name of enhancement because of the damage they predict for values, identities and relationships. Some commentators have even said that adults should not modify themselves through genetic interventions. One commentator worries that genetic modifications chosen by adults for themselves will undermine moral agency, lead to less valuable experiences and fracture people's sense of self. These worries are not justified, however, since the effects of modification will not undo moral agency as such. Adults can still have valuable experiences, even if some prior choices no longer seem meaningful. Changes at the genetic level will not always, either, alienate people from their own sense of self. On the contrary, genetic modifications can help amplify choice, enrich lives and consolidate identities. Ultimately, there is no moral requirement that people value their contingent genetic endowment to the exclusion of changes important to them in their future genetic identities. Through weighing risks and benefits, adults also have the power to consent to, and assume the risks of, genetic modifications for themselves in a way not possible in prenatal genetic interventions.

Synthesis of Monodispersed Ag-Doped Bioactive Glass Nanoparticles via Surface Modification

PubMed Central

Kozon, Dominika; Zheng, Kai; Boccardi, Elena; Liu, Yufang; Liverani, Liliana; Boccaccini, Aldo R.

2016-01-01

Monodispersed spherical Ag-doped bioactive glass nanoparticles (Ag-BGNs) were synthesized by a modified Stöber method combined with surface modification. The surface modification was carried out at 25, 60, and 80 °C, respectively, to investigate the influence of processing temperature on particle properties. Energy-dispersive X-ray spectroscopy (EDS) results indicated that higher temperatures facilitate the incorporation of Ag. Hydroxyapatite (HA) formation on Ag-BGNs was detected upon immersion of the particles in simulated body fluid for 7 days, which indicated that Ag-BGNs maintained high bioactivity after surface modification. The conducted antibacterial assay confirmed that Ag-BGNs had an antibacterial effect on E. coli. The above results thereby suggest that surface modification is an effective way to incorporate Ag into BGNs and that the modified BGNs can remain monodispersed as well as exhibit bioactivity and antibacterial capability for biomedical applications. PMID:28773349

Effect of Cooling Rate and Chemical Modification on the Tensile Properties of Mg-5wt% Si Alloy

NASA Astrophysics Data System (ADS)

Mirshahi, Farshid; Meratian, Mahmood; Zahrani, Mohsen Mohammadi; Zahrani, Ehsan Mohammadi

Hypereutectic Mg-Si alloys are a new class of light materials usable for aerospace and other advanced engineering applications. In this study, the effects of both cooling rate and bismuth modification on the micro structure and tensile properties of hypereutectic Mg-5wt% Si alloy were investigated. It was found that the addition of 0.5% Bi, altered the morphology of primary Mg2Si particles from bulky to polygonal shape and reduced their mean size from more than 70 μm to about 30 (am. Also, the tensile strength and elongation of the modified alloy increased about 10% and 20%, respectively, which should be ascribed to the modification of Mg2Si morphology and more uniform distribution of the primary particles. Moreover, an increase in tensile strength value with increase in cooling rate were observed which is attributed to finer micro structure of alloy in higher cooling rates. It was observed that Bi addition is significantly more effective in refining the morphology of primary Mg2Si particles than applying faster cooling rates.

Small intestinal permeability is increased in diarrhoea predominant IBS, while alterations in gastroduodenal permeability in all IBS subtypes are largely attributable to confounders.

PubMed

Mujagic, Z; Ludidi, S; Keszthelyi, D; Hesselink, M A M; Kruimel, J W; Lenaerts, K; Hanssen, N M J; Conchillo, J M; Jonkers, D M A E; Masclee, A A M

2014-08-01

Intestinal permeability has been studied in small groups of IBS patients with contrasting findings. To assess intestinal permeability at different sites of the GI tract in different subtypes of well-characterised IBS patients and healthy controls (HC), and to assess potential confounding factors. IBS patients and HC underwent a multi-sugar test to assess site-specific intestinal permeability. Sucrose excretion and lactulose/rhamnose ratio in 0-5 h urine indicated gastroduodenal and small intestinal permeability, respectively. Sucralose/erythritol ratio in 0-24 h and 5-24 h urine indicated whole gut and colonic permeability, respectively. Linear regression analysis was used to assess the association between IBS groups and intestinal permeability and to adjust for age, sex, BMI, anxiety or depression, smoking, alcohol intake and use of medication. Ninety-one IBS patients, i.e. 37% IBS-D, 23% IBS-C, 33% IBS-M and 7% IBS-U and 94 HC were enrolled. Urinary sucrose excretion was significantly increased in the total IBS group [μmol, median (Q1;Q3): 5.26 (1.82;11.03) vs. 2.44 (0.91;5.85), P < 0.05], as well as in IBS-C and IBS-D vs. HC. However, differences attenuated when adjusting for confounders. The lactulose/rhamnose ratio was increased in IBS-D vs. HC [0.023 (0.013;0.038) vs. 0.014 (0.008;0.025), P < 0.05], which remained significant after adjustment for confounders. No difference was found in 0-24 and 5-24 h sucralose/erythritol ratio between groups. Small intestinal permeability is increased in patients with IBS-D compared to healthy controls, irrespective of confounding factors. Adjustment for confounders is necessary when studying intestinal permeability, especially in a heterogeneous disorder such as IBS. © 2014 John Wiley & Sons Ltd.

The ethics of molecular memory modification.

PubMed

Hui, Katrina; Fisher, Carl E

2015-07-01

Novel molecular interventions have recently shown the potential to erase, enhance and alter specific long-term memories. Unique features of this form of memory modification call for a close examination of its possible applications. While there have been discussions of the ethics of memory modification in the literature, molecular memory modification (MMM) can provide special insights. Previously raised ethical concerns regarding memory enhancement, such as safety issues, the 'duty to remember', selfhood and personal identity, require re-evaluation in light of MMM. As a technology that exploits the brain's updating processes, MMM helps correct the common misconception that memory is a static entity by demonstrating how memory is plastic and subject to revision even in the absence of external manipulation. Furthermore, while putatively safer than other speculative technologies because of its high specificity, MMM raises notable safety issues, including potential insidious effects on the agent's emotions and personal identity. Nonetheless, MMM possesses characteristics of a more permissible form of modification, not only because it is theoretically safer, but because its unique mechanism of action requires a heightened level of cooperation from the agent. Discussions of memory modification must consider the specific mechanisms of action, which can alter the weight and relevance of various ethical concerns. MMM also highlights the need for conceptual accuracy regarding the term 'enhancement'; this umbrella term will have to be differentiated as new technologies are applied to a widening array of purposes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Historical overview of HF ionospheric modification research

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gordon, W.E.; Duncan, L.M.

1990-10-01

Radio waves have inadvertently modified the Earth's ionosphere since the Luxembourg observations of Tellegen in 1933 and perhaps since Marconi in 1901. The history of ionospheric modification by radio waves is reviewed, beginning with Marconi, describing the Luxembourg effect and its explanations, and its early use to deduce the properties of the lower ionosphere in the 1930s. The measurements became more sophisticated in the 1950s, leading to the call for high-power high-frequency modification experiments in the upper ionosphere. Beginning in 1970, radio facilities became available of sufficient powers to induce changes in the ionospheric plasma detectable by a wide arraymore » of diagnostic instruments and techniques. A summary of these effects is presented based upon work up to 1990. These studies were originally motivated as a means of better understanding the natural ionosphere using a weak perturbational approach. However, a rich spectrum of nonlinear wave-plasma interactions was quickly discovered and ionospheric modification research became strongly motivated by issues in basic plasma physics. The ionosphere and near-Earth space are now exploited as an exceptional plasma laboratory-without-walls for the study of fundamental plasma processes requiring large spatial or temporal scales. Here we present a brief overview of these processes and phenomena, illustrated using results obtained from the Arecibo ionospheric modification facilities. The lessons learned and phenomena explored thus far offer many opportunities for controlling the ionospheric environment critical to many civilian and military telecommunications systems, both to disrupt systems normally operational and to create new propagation paths otherwise unavailable.« less

Genetic modification and genetic determinism

PubMed Central

Resnik, David B; Vorhaus, Daniel B

2006-01-01

In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions. PMID:16800884

Influence of potentially confounding factors on sea urchin porewater toxicity tests

USGS Publications Warehouse

Carr, R.S.; Biedenbach, J.M.; Nipper, M.

2006-01-01

The influence of potentially confounding factors has been identified as a concern for interpreting sea urchin porewater toxicity test data. The results from >40 sediment-quality assessment surveys using early-life stages of the sea urchin Arbacia punctulata were compiled and examined to determine acceptable ranges of natural variables such as pH, ammonia, and dissolved organic carbon on the fertilization and embryological development endpoints. In addition, laboratory experiments were also conducted with A. punctulata and compared with information from the literature. Pore water with pH as low as 6.9 is an unlikely contributor to toxicity for the fertilization and embryological development tests with A. punctulata. Other species of sea urchin have narrower pH tolerance ranges. Ammonia is rarely a contributing factor in pore water toxicity tests using the fertilization endpoint, but the embryological development endpoint may be influenced by ammonia concentrations commonly found in porewater samples. Therefore, ammonia needs to be considered when interpreting results for the embryological development test. Humic acid does not affect sea urchin fertilization at saturation concentrations, but it could have an effect on the embryological development endpoint at near-saturation concentrations. There was no correlation between sediment total organic carbon concentrations and porewater dissolved organic carbon concentrations. Because of the potential for many varying substances to activate parthenogenesis in sea urchin eggs, it is recommended that a no-sperm control be included with every fertilization test treatment. ?? 2006 Springer Science+Business Media, Inc.

Gait modification strategies for altering medial knee joint load: a systematic review.

PubMed

Simic, Milena; Hinman, Rana S; Wrigley, Tim V; Bennell, Kim L; Hunt, Michael A

2011-03-01

To evaluate the effect of gait modification strategies on the external knee adduction moment (KAM), a marker of medial knee joint load; determine potentially adverse effects; assess the methodologic quality; and identify areas of future research. Five electronic databases were searched. Studies evaluating the effects of gait modifications on the KAM in either healthy individuals or those with knee osteoarthritis (OA) were included. Methodologic quality was evaluated by 2 reviewers using the Downs and Black checklist. Twenty-four studies met the inclusion criteria, exploring 14 different gait modifications of varying sample sizes, age groups, and OA classifications. Contralateral cane use, increased step width, medial knee thrust, increased hip internal rotation, weight transfer to the medial foot, and increased lateral trunk lean demonstrated KAM reductions. Tai Chi gait, ipsilateral cane use, Nordic walking poles, and increased knee flexion exhibited increases in the KAM, demonstrating a potential detriment to their use. The effects of reduced stride length, as well as increases and reductions in either toe-out or gait speed, were inconsistent across the studies and gait cycle. This review demonstrates that some gait modifications have the ability to alter knee load. Future research is required to determine the magnitude of modification required to maximize beneficial effects, the best method of training, long-term patient adherence, and if these biomechanical changes can translate into clinically relevant changes in symptoms or disease progression risk. Copyright © 2011 by the American College of Rheumatology.

Parametric mediational g-formula approach to mediation analysis with time-varying exposures, mediators, and confounders

PubMed Central

Lin, Sheng-Hsuan; Young, Jessica; Logan, Roger; Tchetgen Tchetgen, Eric J.; VanderWeele, Tyler J.

2016-01-01

The assessment of direct and indirect effects with time-varying mediators and confounders is a common but challenging problem, and standard mediation analysis approaches are generally not applicable in this context. The mediational g-formula was recently proposed to address this problem, paired with a semi-parametric estimation approach to evaluate longitudinal mediation effects empirically. In this paper, we develop a parametric estimation approach to the mediational g-formula, including a feasible algorithm implemented in a freely available SAS macro. In the Framingham Heart Study data, we apply this method to estimate the interventional analogues of natural direct and indirect effects of smoking behaviors sustained over a 10-year period on blood pressure when considering weight change as a time-varying mediator. Compared with not smoking, smoking 20 cigarettes per day for 10 years was estimated to increase blood pressure by 1.2 (95 % CI: −0.7, 2.7) mm-Hg. The direct effect was estimated to increase blood pressure by 1.5 (95 % CI: −0.3, 2.9) mm-Hg, and the indirect effect was −0.3 (95% CI: −0.5, −0.1) mm-Hg, which is negative because smoking which is associated with lower weight is associated in turn with lower blood pressure. These results provide evidence that weight change in fact partially conceals the detrimental effects of cigarette smoking on blood pressure. Our work represents, to our knowledge, the first application of the parametric mediational g-formula in an epidemiologic cohort study. PMID:27984420

Evaluation of cab car crashworthiness design modifications

DOT National Transportation Integrated Search

1997-03-01

A study was conducted to evaluate the effectiveness of structural : modifications to rail cab cars for increased crashworthiness protection in train collisions. The crashworthiness benefits were calculated based on a particular design's ability to pr...

[Surface modifications of titanium implant material with excimer laser for more effective osseointegration].

PubMed

Pelsoczi, Kovács István; Bereznai, Miklós; Tóth, Zsolt; Turzó, Kinga; Radnai, Márta; Bor, Zsolt; Fazekas, András

2004-12-01

The biointegration of dental and orthopaedic implants depends mainly on the morphology and physical-chemical properties of their surfaces. Accordingly, the development of the desired microstructure is a relevant requirement in the bulk manufacture. Besides the widely used sandblasting plus acid etching and plasma-spray coating techniques, the laser surface modification method offers a plausible alternative. In order to analyze the influence of the laser treatment, the surfaces of titanium samples were exposed to excimer laser irradiation. The aim of this study was to develop surfaces that provide optimal conditions for bone-implant contact, bone growth, formation and maintenance of gingival attachment. For this purpose, holes were ablated on the surface of samples by nanosecond (18 ns, ArF) and also sub-picosecond (0,5 ps, KrF) laser pulses. Using pulses of ns length, due to melt ejection, crown-like protrusions were formed at the border of the holes, which made them sensitive to mechanical effects. To avoid these undesirable crown-like structures ultrashort KrF excimer laser pulses were successfully applied. On the other hand, titanium samples were laser-polished in favour of formation and connection of healthy soft tissues. Irradiation by a series of nanosecond laser pulses resulted in an effective smoothening as detected by atomic force microscopy (AFM). By inhibiting plaque accumulation this favours formation of gingival attachment. X-ray photoelectron spectroscopy (XPS) studies showed that laser treatment, in addition to micro-structural and morphological modification, results in decreasing of surface contamination and thickening of the oxide layer. X-ray diffraction (XRD) analysis revealed that the original alpha-titanium crystalline structure of the laser-polished titanium surface was not altered by the irradiation.

The relationship between type D personality and chronic heart failure is not confounded by disease severity as assessed by BNP.

PubMed

Pelle, Aline J; van den Broek, Krista C; Szabó, Balázs; Kupper, Nina

2010-11-05

Psychological factors, like Type D personality (i.e., the tendency to experience negative emotions and to inhibit emotional distress) have been linked to impaired health outcomes. Criticism on the role of psychological factors in cardiac disease has postulated that such constructs may be confounded by disease severity. Hence, we examined whether Type D personality is associated with brain natriuretic peptide (BNP), a sensitive marker of disease severity in chronic heart failure (CHF), in 202 consecutive CHF outpatients. No differences in logBNP levels were found between Type D and non-Type D patients (t(200) = -1.03, p = .30). After adjusting for demographic and clinical confounders, Type D personality remained unassociated with logBNP levels (β=.04, p = .55), whereas older age (β = .27, p<.001), being prescribed beta-blockers (β = .15, p = .02), lower left ventricular ejection fraction (β = -.38, p<.0001), and kidney dysfunction (β = .17, p = .01) were associated with higher logBNP. To conclude, Type D personality was not associated with BNP in CHF outpatients, whereas clinical variables were associated with BNP. These findings oppose the suggestion that Type D personality is confounded by indicators of disease severity. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Detection rates of geckos in visual surveys: Turning confounding variables into useful knowledge

USGS Publications Warehouse

Lardner, Bjorn; Rodda, Gordon H.; Yackel Adams, Amy A.; Savidge, Julie A.; Reed, Robert N.

2016-01-01

Transect surveys without some means of estimating detection probabilities generate population size indices prone to bias because survey conditions differ in time and space. Knowing what causes such bias can help guide the collection of relevant survey covariates, correct the survey data, anticipate situations where bias might be unacceptably large, and elucidate the ecology of target species. We used negative binomial regression to evaluate confounding variables for gecko (primarily Hemidactylus frenatus and Lepidodactylus lugubris) counts on 220-m-long transects surveyed at night, primarily for snakes, on 9,475 occasions. Searchers differed in gecko detection rates by up to a factor of six. The worst and best headlamps differed by a factor of at least two. Strong winds had a negative effect potentially as large as those of searchers or headlamps. More geckos were seen during wet weather conditions, but the effect size was small. Compared with a detection nadir during waxing gibbous (nearly full) moons above the horizon, we saw 28% more geckos during waning crescent moons below the horizon. A sine function suggested that we saw 24% more geckos at the end of the wet season than at the end of the dry season. Fluctuations on a longer timescale also were verified. Disturbingly, corrected data exhibited strong short-term fluctuations that covariates apparently failed to capture. Although some biases can be addressed with measured covariates, others will be difficult to eliminate as a significant source of error in longterm monitoring programs.

Cellular GFP Toxicity and Immunogenicity: Potential Confounders in in Vivo Cell Tracking Experiments.

PubMed

Ansari, Amir Mehdi; Ahmed, A Karim; Matsangos, Aerielle E; Lay, Frank; Born, Louis J; Marti, Guy; Harmon, John W; Sun, Zhaoli

2016-10-01

Green Fluorescent protein (GFP), used as a cellular tag, provides researchers with a valuable method of measuring gene expression and cell tracking. However, there is evidence to suggest that the immunogenicity and cytotoxicity of GFP potentially confounds the interpretation of in vivo experimental data. Studies have shown that GFP expression can deteriorate over time as GFP tagged cells are prone to death. Therefore, the cells that were originally marked with GFP do not survive and cannot be accurately traced over time. This review will present current evidence for the immunogenicity and cytotoxicity of GFP in in vivo studies by characterizing these responses.

[Evaluation on cost-effectiveness of snail control project by environmental modification in hilly regions].

PubMed

Li, Shui-Ming; Chen, Shi-Jun; Wu, Xiao-Jun; Chen, Xi-Qing; Zhang, Rong-Ping; Zhang, Jian-Rong

2011-02-01

To evaluate the cost-effectiveness of the snail control project by environmental modification in order to provide the evidence for quickly interrupting the transmission of schistosomiasis in hilly regions. Field investigations were carried out. The changes of the snail habitat areas were compared before and after the snail control project. The direct costs of the snail control were calculated. The reduction rates of snail area and snail density were regarded as the evaluation indexes of the effectiveness. The costs for reduction of 1% of snail area and 1% of snail density were used as the unit for cost-effectiveness analysis. After the 15 projects were implemented, there were no snails in 12 areas. The reduction rates of snail areas were 72.22% to 100%. The reduction rates of the snail area and density were both 100% in the areas with digging new ditches to fill up the old ones and building reservoirs. The total cost of 15 projects was 1 450 800 Yuan. The average cost per unit was 0.56 Yuan/m2. After the snail control project by digging new ditches to fill up the old ones was implemented, the costs of snail area and density decreased by one unit were 300 -700 Yuan, by building reservoirs, the costs were 600 -2 600 Yuan, by building fishpond, the costs were 1 200 - 1 500 Yuan, by watershed comprehensive measures, the costs were 900 - 2 700 Yuan. The cost of digging new ditches to fill up the old ones was significantly lower than that of building reservoirs or watershed comprehensive measures, but there was no significant difference between building reservoirs and watershed comprehensive measures. In hilly regions, the implementation of snail control project by environmental modification combined with construction of water conservancy is effective, and the cost-effectiveness of the snail control with digging new ditches to fill up the old ones is excellent.

Augmented liver targeting of exosomes by surface modification with cationized pullulan.

PubMed

Tamura, Ryo; Uemoto, Shinji; Tabata, Yasuhiko

2017-07-15

Exosomes are membrane nanoparticles containing biological substances that are employed as therapeutics in experimental inflammatory models. Surface modification of exosomes for better tissue targetability and enhancement of their therapeutic ability was recently attempted mainly using gene transfection techniques. Here, we show for the first time that the surface modification of exosomes with cationized pullulan, which has the ability to target hepatocyte asialoglycoprotein receptors, can target injured liver and enhance the therapeutic effect of exosomes. Surface modification can be achieved by a simple mixing of original exosomes and cationized pullulan and through an electrostatic interaction of both substances. The exosomes modified with cationized pullulan were internalized into HepG2 cells in vitro to a significantly greater extent than unmodified ones and this internalization was induced through the asialoglycoprotein receptor that was specifically expressed on HepG2 cells and hepatocytes. When injected intravenously into mice with concanavalin A-induced liver injury, the modified exosomes accumulated in the liver tissue, resulting in an enhanced anti-inflammatory effect in vivo. It is concluded that the surface modification with cationized pullulan promoted accumulation of the exosomes in the liver and the subsequent biological function, resulting in a greater therapeutic effect on liver injury. Exosomes have shown potentials as therapeutics for various inflammatory disease models. This study is the first to show the specific accumulation of exosomes in the liver and enhanced anti-inflammatory effect via the surface modification of exosomes using pullulan, which is specifically recognized by the asialoglycoprotein receptor (AGPR) on HepG2 cells and hepatocytes. The pullulan was expressed on the surface of PKH-labeled exosomes, and it led increased accumulation of PKH into HepG2 cells, whereas the accumulation was canceled by AGPR inhibitor. In the mouse

Epigenetic modifications in prostate cancer.

PubMed

Ngollo, Marjolaine; Dagdemir, Aslihan; Karsli-Ceppioglu, Seher; Judes, Gaelle; Pajon, Amaury; Penault-Llorca, Frederique; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique J

2014-01-01

Prostate cancer is the most common cancer in men and the second leading cause of cancer deaths in men in France. Apart from the genetic alterations in prostate cancer, epigenetics modifications are involved in the development and progression of this disease. Epigenetic events are the main cause in gene regulation and the three most epigenetic mechanisms studied include DNA methylation, histone modifications and microRNA expression. In this review, we summarized epigenetic mechanisms in prostate cancer. Epigenetic drugs that inhibit DNA methylation, histone methylation and histone acetylation might be able to reactivate silenced gene expression in prostate cancer. However, further understanding of interactions of these enzymes and their effects on transcription regulation in prostate cancer is needed and has become a priority in biomedical research. In this study, we summed up epigenetic changes with emphasis on pharmacologic epigenetic target agents.

Ambient air pollution and completed suicide in 26 South Korean cities: Effect modification by demographic and socioeconomic factors.

PubMed

Lee, Hyewon; Myung, Woojae; Kim, Satbyul Estella; Kim, Doh Kwan; Kim, Ho

2018-10-15

Air pollution has been recently associated with suicide mortality. However, limited studies have examined possible effect modification of the association by various demographic and socioeconomic factors, despite their crucial roles on suicide risk. In 73,445 completed suicide cases from 26 South Korean cities from 2002 to 2013, we studied the association of suicide risk with exposure to particles <10 μm (PM 10 ), nitrogen dioxide (NO 2 ), sulfur dioxide (SO 2 ), ozone (O 3 ), and carbon monoxide (CO), using a city-specific conditional logistic regression analysis with a case-crossover design. Random effects meta-analysis was used to pool the results. We considered a delayed effect of air pollution by constructing lags of up to 7 days. We explored effect modification by demographic and socioeconomic factors (sex, age, education level, job, and marital status) as well as place of death, method of suicide, and season, through stratified subgroup analyses. Among five pollutants, NO 2 showed the strongest association at immediate lags (percent change in odds ratio; PM 10 : 1.2% [95% CI, 0.2%, 2.3%]; NO 2 : 4.3% [95% CI, 1.9%, 6.7%]; SO 2 : 2.2% [95% CI, 0.7%, 3.8%]; O 3 : 1.5% [95% CI, -0.3%, 3.2%]; and CO: 2.4% [95% CI, 0.9%, 3.8%] per interquartile range increase at lag0). In subgroup analyses by socioeconomic factors, stronger associations were observed in the male sex, the elderly, those with lower education status, white-collar workers, and the married; the largest association was an 11.0% increase (95% CI, 4.1%, 18.4%) by NO 2 among white-collar workers. We add evidence of effect modification of the association between air pollution exposure and suicide risk by various demographic and socioeconomic factors. These findings can serve as the basis for suicide prevention strategies by providing information regarding susceptible subgroups. Copyright © 2018 Elsevier B.V. All rights reserved.

Permit application modifications

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1995-11-01

This document contains the Permit Application Modifications for the Y-12 Industrial Landfill V site on the Oak Ridge Reservation. These modifications include the assessment of stability of the proposed Landfill V under static and loading conditions. Analyses performed include the general slope stability, veneer stability of the bottom liner and cover system, and a liquefaction potential assessment of the foundation soils.

Effects of proposed highway embankment modifications on water-surface elevations in the lower Pearl River flood plain near Slidell, Louisiana

USGS Publications Warehouse

Gilbert, J.J.; Schuck-Kolben, R. E.

1987-01-01

Major flooding in the lower Pearl River basin in recent years has caused extensive damage to homes and highways in the area. In 1980 and 1983, Interstate Highway 10 and U.S. Highway 190 were overtopped. In 1983, the Interstate Highway 10 crossing was seriously damaged by the flood. The U.S. Geological Survey, in cooperation with the Louisiana Department of Transportation and Development, Office of Highways, used a two-dimensional finite-element surface-water flow model to evaluate the effects the proposed embankment modifications at Interstate Highway 10 and U.S. Highway 90 on the water-surface elevations in the lower Pearl River flood plain near Slidell, Louisiana. The proposed modifications that were considered for the 1983 flood are: (1) Removal of all highway embankments, the natural condition, (2) extension of the West Pearl River bridge by 1,000 feet at U.S. Highway 90, (3) construction of a new 250-foot bridge opening in the U.S. Highways 190 and 90, west of the intersection of the highways. The proposed highway bridge modifications also incorporated lowering of ground-surface elevations under the new bridges to sea level. The modification that provided the largest reduction in backwater, about 35 percent, was a new bridge in Interstate Highway 10. The modification of the West Pearl River bridge at U.S. Highway 90 and replacement of the bridge in U.S. Highway 190 provide about a 25% reduction in backwater each. For the other modification conditions that required structural modifications, maximum backwater computed on the west side of the flood plain ranges from 0.0 to 0.8 foot and on the east side from 0.0 to 0.6 foot. Results show that although backwater is greater on the west side of the flood plain than on the east side, upstream of highway embankments, backwater decreases more rapidly in the upstream direction on the west side of the flood plain than on the east side. Analysis of the proposed modifications indicates that backwater would still occur on

Surface layer modification of ion bombarded HDPE

NASA Astrophysics Data System (ADS)

Bielinski, D.; Lipinski, P.; Slusarski, L.; Grams, J.; Paryjczak, T.; Jagielski, J.; Turos, A.; Madi, N. K.

2004-08-01

Press-moulded, high density polyethylene (HDPE) samples were subjected to ion bombardment and effects of the modification studied. He + ions of energy 100 keV or Ar + ions of energy 130 keV were applied in the range of dose 1-30 × 10 15/cm 2 or 1-100 × 10 14/cm 2, respectively. This paper has been focused on structural changes of the surface layer. The consequences of the modification were studied with TOF-SIMS and FTIR-IRS techniques. The results point on two mechanisms taking place simultaneously: ionization of polymer macromolecules and chain scission--resulting in creation of macroradicals. Both of them produce oxidation and lead to significant release of hydrogen. The former diminishes for the highest ion doses, however, creation of molecular oxygen cannot be excluded. The latter in the case of Ar + ion bombardment is reflected by prevailing degradation of the surface layer of HDPE. Contrary to the effect of heavy ions, He + ion bombardment was found to produce significant increase of the material hardness, which was explained by crosslinking of polyethylene. A mechanism of polyacetylene formation, proceeding finally to cross-polymerization of the polymer was proposed. Apart from structural changes, the modification revealed additionally a possibility to improve the wettability of the polymer.

14 CFR 420.47 - License modification.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false License modification. 420.47 Section 420.47 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF... approval has the full force and effect of a license order and is part of the licensing record. ...

14 CFR 420.47 - License modification.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false License modification. 420.47 Section 420.47 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF... approval has the full force and effect of a license order and is part of the licensing record. ...

14 CFR 420.47 - License modification.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false License modification. 420.47 Section 420.47 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF... approval has the full force and effect of a license order and is part of the licensing record. ...

Is it patience or motivation? On motivational confounds in intertemporal choice tasks.

PubMed

Paglieri, Fabio; Addessi, Elsa; Sbaffi, Agnese; Tasselli, Maria Isabella; Delfino, Alexia

2015-01-01

Intertemporal choices create a tension between amount maximization, which would favor the larger and later option (LL), and delay minimization, which would promote the smaller and sooner reward (SS). Two common interpretations of intertemporal choice behavior are discussed: looking at LL responses as indicative of self-control, and using intertemporal choices to assess delay aversion. We argue that both interpretations need to take into account motivational confounds, in order to be warranted by data. In intertemporal choices with prepotent, salient stimuli (e.g., food amounts, typically used with nonhuman primates), LL responses could also be indicative of failed inhibition of a "go for more" impulsive response-the opposite of self-control. Similarly, intertemporal choices can be used to measure delay aversion only with respect to the subject's baseline motivation to maximize the reinforcer in question, and this baseline is not always assessed in current experimental protocols. This concern is especially crucial in comparing intertemporal choices across different groups or manipulation. We focus in particular on the effects of reward types on intertemporal choices, presenting two experimental studies where the difference in behavior with monetary versus food rewards is the product of different baseline motivation, rather than variations in delay aversion. We conclude discussing the implications of these and other similar recent findings, which are far-reaching. © Society for the Experimental Analysis of Behavior.

Behavior Modification in Coaching.

ERIC Educational Resources Information Center

Lynch, Annette Rutt; Stillman, Stephen M.

1979-01-01

An example of behavior modification used in athletic coaching is presented. The case study involves a member of a women's basketball team and details the use of behavior modification for both weight reduction and skill improvement. (JMF)

Offspring ADHD as a risk factor for parental marital problems: controls for genetic and environmental confounds.

PubMed

Schermerhorn, Alice C; D'Onofrio, Brian M; Slutske, Wendy S; Emery, Robert E; Turkheimer, Eric; Harden, K Paige; Heath, Andrew C; Martin, Nicholas G

2012-12-01

Previous studies have found that child attention-deficit/hyperactivity disorder (ADHD) is associated with more parental marital problems. However, the reasons for this association are unclear. The association might be due to genetic or environmental confounds that contribute to both marital problems and ADHD. Data were drawn from the Australian Twin Registry, including 1,296 individual twins, their spouses, and offspring. We studied adult twins who were discordant for offspring ADHD.Using a discordant twin pairs design, we examined the extent to which genetic and environmental confounds,as well as measured parental and offspring characteristics, explain the ADHD-marital problems association. Offspring ADHD predicted parental divorce and marital conflict. The associations were also robust when comparing differentially exposed identical twins to control for unmeasured genetic and environmental factors, when controlling for measured maternal and paternal psychopathology,when restricting the sample based on timing of parental divorce and ADHD onset, and when controlling for other forms of offspring psychopathology. Each of these controls rules out alternative explanations for the association. The results of the current study converge with those of prior research in suggesting that factors directly associated with offspring ADHD increase parental marital problems.

Offspring ADHD as a Risk Factor for Parental Marital Problems: Controls for Genetic and Environmental Confounds

PubMed Central

Schermerhorn, Alice C.; D’Onofrio, Brian M.; Slutske, Wendy S.; Emery, Robert E.; Turkheimer, Eric; Harden, K. Paige; Heath, Andrew C.; Martin, Nicholas G.

2013-01-01

Background Previous studies have found that child attention-deficit/hyperactivity disorder (ADHD) is associated with more parental marital problems. The reasons for this association are unclear, however. The association might be due to genetic or environmental confounds that contribute to both marital problems and ADHD. Method Data were drawn from the Australian Twin Registry, including 1296 individual twins, their spouses, and offspring. We studied adult twins who were discordant for offspring ADHD. Using a discordant twin pairs design, we examined the extent to which genetic and environmental confounds, as well as measured parental and offspring characteristics, explain the ADHD-marital problems association. Results Offspring ADHD predicted parental divorce and marital conflict. The associations were also robust when comparing differentially exposed identical twins to control for unmeasured genetic and environmental factors, when controlling for measured maternal and paternal psychopathology, when restricting the sample based on timing of parental divorce and ADHD onset, and when controlling for other forms of offspring psychopathology. Each of these controls rules out alternative explanations for the association. Conclusion The results of the current study converge with those of prior research in suggesting that factors directly associated with offspring ADHD increase parental marital problems. PMID:22958575

Diagnostic confounders of chronic widespread pain: not always fibromyalgia

PubMed Central

Häuser, Winfried; Perrot, Serge; Sommer, Claudia; Shir, Yoram; Fitzcharles, Mary-Ann

2017-01-01

Abstract Introduction: Chronic widespread pain (CWP) is the defining feature of fibromyalgia (FM), a worldwide prevalent condition. Chronic widespread pain is, however, not pathognomonic of FM, and other conditions may present similarly with CWP, requiring consideration of a differential diagnosis. Objectives: To conduct a literature search to identify medical conditions that may mimic FM and have highlighted features that may differentiate these various conditions from FM. Methods: A comprehensive literature search from 1990 through September 2016 was conducted to identify conditions characterized by CWP. Results: Conditions that may mimic FM may be categorized as musculoskeletal, neurological, endocrine/metabolic, psychiatric/psychological, and medication related. Characteristics pertaining to the most commonly identified confounding diagnoses within each category are discussed; clues to enable clinical differentiation from FM are presented; and steps towards a diagnostic algorithm for mimicking conditions are presented. Conclusion: Although the most likely reason for a complaint of CWP is FM, this pain complaint can be a harbinger of illness other than FM, prompting consideration of a differential diagnosis. This review should sensitize physicians to a broad spectrum of conditions that can mimic FM. PMID:29392213

Microscale surface modifications for heat transfer enhancement.

PubMed

Bostanci, Huseyin; Singh, Virendra; Kizito, John P; Rini, Daniel P; Seal, Sudipta; Chow, Louis C

2013-10-09

In this experimental study, two surface modification techniques were investigated for their effect on heat transfer enhancement. One of the methods employed the particle (grit) blasting to create microscale indentations, while the other used plasma spray coating to create microscale protrusions on Al 6061 (aluminum alloy 6061) samples. The test surfaces were characterized using scanning electron microscopy (SEM) and confocal scanning laser microscopy. Because of the surface modifications, the actual surface area was increased up to 2.8× compared to the projected base area, and the arithmetic mean roughness value (Ra) was determined to vary from 0.3 μm for the reference smooth surface to 19.5 μm for the modified surfaces. Selected samples with modified surfaces along with the reference smooth surface were then evaluated for their heat transfer performance in spray cooling tests. The cooling system had vapor-atomizing nozzles and used anhydrous ammonia as the coolant in order to achieve heat fluxes up to 500 W/cm(2) representing a thermal management setting for high power systems. Experimental results showed that the microscale surface modifications enhanced heat transfer coefficients up to 76% at 500 W/cm(2) compared to the smooth surface and demonstrated the benefits of these practical surface modification techniques to enhance two-phase heat transfer process.

Edge and area effects on the occurrence of migrant forest songbirds

USGS Publications Warehouse

Parker, T.H.; Stansberry, B.M.; Becker, C.D.; Gipson, P.S.

2005-01-01

Concerns about forest fragmentation and its conservation implications have motivated numerous studies that investigate the influence of forest patch area and forest edge on songbird distribution patterns. The generalized effects of forest patch size and forest edge on animal distributions is still debatable because forest patch size and forest edge are often confounded and because of an incomplete synthesis of available data. To fill a portion of this gap, we incorporated all available published data (33 papers) in meta-analyses of forest edge and area effects on site occupancy patterns for 26 Neotropical migrant forest-nesting songbirds in eastern North America. All reported area effects are confounded or potentially confounded by edge effects, and we refer to these as "confounded" studies. The converse, however, is not true and most reported edge effects are independent of patch area. When considering only nonconfounded studies of edge effects, only 1 of 17 species showed significant edge avoidance and 3 had significant affinity for edges. In confounded studies, 12 of 22 species showed significant avoidance of small patches and edges, and 1 had an affinity for small patches and edges. Furthermore, average effect sizes averaged across studies or species tended to be higher for confounded studies than for edge studies. We discuss three possible reasons for differences in results between these two groups of studies. First, studies of edge effects tended to be carried out in landscapes with greater forest cover than studies of confounded effects; among confounded effects studies, as forest cover increased, we observed a nonsignificant trend towards decreasing strength of small patch or edge avoidance effects. Thus, the weaker effects in edge studies may be due to the fact that these studies were conducted in forest-dominated landscapes. Second, we may have detected strong effects only in confounded studies because area effects are much stronger than edge effects on

Attention bias for chocolate increases chocolate consumption--an attention bias modification study.

PubMed

Werthmann, Jessica; Field, Matt; Roefs, Anne; Nederkoorn, Chantal; Jansen, Anita

2014-03-01

The current study examined experimentally whether a manipulated attention bias for food cues increases craving, chocolate intake and motivation to search for hidden chocolates. To test the effect of attention for food on subsequent chocolate intake, attention for chocolate was experimentally modified by instructing participants to look at chocolate stimuli ("attend chocolate" group) or at non-food stimuli ("attend shoes" group) during a novel attention bias modification task (antisaccade task). Chocolate consumption, changes in craving and search time for hidden chocolates were assessed. Eye-movement recordings were used to monitor the accuracy during the experimental attention modification task as possible moderator of effects. Regression analyses were conducted to test the effect of attention modification and modification accuracy on chocolate intake, craving and motivation to search for hidden chocolates. Results showed that participants with higher accuracy (+1 SD), ate more chocolate when they had to attend to chocolate and ate less chocolate when they had to attend to non-food stimuli. In contrast, for participants with lower accuracy (-1 SD), the results were exactly reversed. No effects of the experimental attention modification on craving or search time for hidden chocolates were found. We used chocolate as food stimuli so it remains unclear how our findings generalize to other types of food. These findings demonstrate further evidence for a link between attention for food and food intake, and provide an indication about the direction of this relationship. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cigarette smoking and endometrial carcinoma risk: the role of effect modification and tumor heterogeneity

PubMed Central

Yang, Hannah P.; Gierach, Gretchen L.; Park, Yikyung; Brinton, Louise A.

2014-01-01

Purpose The inverse relationship between cigarette smoking and endometrial carcinoma risk is well established. We examined effect modification of this relationship and associations with tumor characteristics in the National Institutes of Health–AARP Diet and Health Study. Methods We examined the association between cigarette smoking and endometrial carcinoma risk among 110,304 women. During 1,029,041 person years of follow-up, we identified 1,476 incident endometrial carcinoma cases. Multivariable Cox proportional hazards regression models were used to estimate relative risks (RRs) and 95 % confidence intervals (CIs) for the association between smoking status, years since smoking cessation, and endometrial carcinoma risk overall and within strata of endometrial carcinoma risk factors. Effect modification was assessed using likelihood ratio test statistics. Smoking associations by histologic subtype/grade and stage at diagnosis were also evaluated. Results Reduced endometrial carcinoma risk was evident among former (RR 0.89, 95 % CI 0.80, 1.00) and current (RR 0.65, 95 % CI 0.55, 0.78) smokers compared with never smokers. Smoking cessation 1–4 years prior to baseline was significantly associated with endometrial carcinoma risk (RR 0.65, 95 % CI 0.48, 0.89), while cessation ≥10 years before baseline was not. The association between smoking and endometrial carcinoma risk was not significantly modified by any endometrial carcinoma risk factor, nor did we observe major differences in risk associations by tumor characteristics. Conclusion The cigarette smoking–endometrial carcinoma risk relationship was consistent within strata of important endometrial carcinoma risk factors and by clinically relevant tumor characteristics. PMID:24487725

Cascaded discrimination of normal, abnormal, and confounder classes in histopathology: Gleason grading of prostate cancer

PubMed Central

2012-01-01

Background Automated classification of histopathology involves identification of multiple classes, including benign, cancerous, and confounder categories. The confounder tissue classes can often mimic and share attributes with both the diseased and normal tissue classes, and can be particularly difficult to identify, both manually and by automated classifiers. In the case of prostate cancer, they may be several confounding tissue types present in a biopsy sample, posing as major sources of diagnostic error for pathologists. Two common multi-class approaches are one-shot classification (OSC), where all classes are identified simultaneously, and one-versus-all (OVA), where a “target” class is distinguished from all “non-target” classes. OSC is typically unable to handle discrimination of classes of varying similarity (e.g. with images of prostate atrophy and high grade cancer), while OVA forces several heterogeneous classes into a single “non-target” class. In this work, we present a cascaded (CAS) approach to classifying prostate biopsy tissue samples, where images from different classes are grouped to maximize intra-group homogeneity while maximizing inter-group heterogeneity. Results We apply the CAS approach to categorize 2000 tissue samples taken from 214 patient studies into seven classes: epithelium, stroma, atrophy, prostatic intraepithelial neoplasia (PIN), and prostate cancer Gleason grades 3, 4, and 5. A series of increasingly granular binary classifiers are used to split the different tissue classes until the images have been categorized into a single unique class. Our automatically-extracted image feature set includes architectural features based on location of the nuclei within the tissue sample as well as texture features extracted on a per-pixel level. The CAS strategy yields a positive predictive value (PPV) of 0.86 in classifying the 2000 tissue images into one of 7 classes, compared with the OVA (0.77 PPV) and OSC approaches (0.76 PPV

Familial confounding of the association between maternal smoking during pregnancy and offspring substance use and problems.

PubMed

D'Onofrio, Brian M; Rickert, Martin E; Langström, Niklas; Donahue, Kelly L; Coyne, Claire A; Larsson, Henrik; Ellingson, Jarrod M; Van Hulle, Carol A; Iliadou, Anastasia N; Rathouz, Paul J; Lahey, Benjamin B; Lichtenstein, Paul

2012-11-01

Previous epidemiological, animal, and human cognitive neuroscience research suggests that maternal smoking during pregnancy (SDP) causes increased risk of substance use/problems in offspring. To determine the extent to which the association between SDP and offspring substance use/problems depends on confounded familial background factors by using a quasi-experimental design. We used 2 separate samples from the United States and Sweden. The analyses prospectively predicted multiple indices of substance use and problems while controlling for statistical covariates and comparing differentially exposed siblings to minimize confounding. Offspring of a representative sample of women in the United States (sample 1) and the total Swedish population born during the period from January 1, 1983, to December 31, 1995 (sample 2). Adolescent offspring of the women in the National Longitudinal Survey of Youth 1979 (n = 6904) and all offspring born in Sweden during the 13-year period (n = 1,187,360). Self-reported adolescent alcohol, cigarette, and marijuana use and early onset (before 14 years of age) of each substance (sample 1) and substance-related convictions and hospitalizations for an alcohol- or other drug-related problem (sample 2). The same pattern emerged for each index of substance use/problems across the 2 samples. At the population level, maternal SDP predicted every measure of offspring substance use/problems in both samples, ranging from adolescent alcohol use (hazard ratio [HR](moderate), 1.32 [95% CI, 1.22-1.43]; HR(high), 1.33 [1.17-1.53]) to a narcotics-related conviction (HR(moderate), 2.23 [2.14-2.31]; HR(high), 2.97 [2.86-3.09]). When comparing differentially exposed siblings to minimize genetic and environmental confounds, however, the association between SDP and each measure of substance use/problems was minimal and not statistically significant. The association between maternal SDP and offspring substance use/problems is likely due to familial background

Effects of different surface modification and contents on municipal solid waste incineration fly ash/epoxy composites.

PubMed

Goh, C K; Valavan, S E; Low, T K; Tang, L H

2016-12-01

Incineration fly ash, a waste from municipal solid waste incineration plant can be used to replace conventional filler as reinforcing filler to enhance the mechanical strength of a composite. Surface modification was performed on the incineration fly ash before mixing into the soft polymer matrix so as to improve interfacial bond of the filler and epoxy resin. In this study, detailed characterisation of mechanical, morphological and leaching behaviours of municipal solid waste incineration (MSWI) fly ash infused composite has been carried out. Flexural and tensile test was conducted to determine the effect on mechanical properties of the composite by varying the concentration of incineration fly ash filler added into polymer matrix and surface modification of incineration fly ash filler using silane coupling agent and colloidal mesoporous silica (CMS). The results indicated that composite infused with incineration fly ash filler surface treated with CMS shown improvement on the tensile and flexural strengths. In addition, SEM images showed that surface modification of incineration fly ash with colloidal mesoporous silica enhanced the interfacial bonding with polymer resin which explained the improvement of mechanical strength. Leaching test showed result of toxic metals such as Pb, Zn, Fe, Cu, Cr, Cd and Rb immobilised in the polymer matrix of the composite. Hence, the use of MSWI fly ash as reinforcing filler in the composite appears green and sustainable because this approach is a promising opportunity to substitute valuable raw material with MSWI fly ash. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ammonia modification for flotation separation of polycarbonate and polystyrene waste plastics.

PubMed

Wang, Chong-Qing; Wang, Hui; Gu, Guo-Hua; Lin, Qing-Quan; Zhang, Ling-Ling; Huang, Luo-Luo; Zhao, Jun-Yao

2016-05-01

A promising method, ammonia modification, was developed for flotation separation of polycarbonate (PC) and polystyrene (PS) waste plastics. Ammonia modification has little effect on flotation behavior of PS, while it changes significantly that of PC. The PC recovery in the floated product drops from 100% to 3.17% when modification time is 13min and then rises to 100% after longer modification. The mechanism of ammonia modification was studied by contact angle, and Fourier transform infrared (FT-IR) and X-ray photoelectron spectroscopy (XPS) measurements. Contact angle of PC indicates the decline of PC recovery in the floated product is ascribed to an increase in surface wettability. FT-IR and XPS spectra suggest that ammonia modification causes chemical reactions occurred on PC surface. Flotation behavior of ammonia-modified PC and PS was investigated with respect to flotation time, frother concentration and particle sizes. Flotation separation of PC and PS waste plastics was conducted based on the flotation behavior of single plastic. PC and PS mixtures with different particle sizes are separated efficiently, implying that the technology possesses superior applicability to particle sizes of plastics. The purity of PS and PC is up to 99.53% and 98.21%, respectively, and the recovery of PS and PC is larger than 92.06%. A reliable, cheap and effective process is proposed for separation of PC and PS waste plastics. Copyright © 2016 Elsevier Ltd. All rights reserved.

[The effects of a physical activity-behavior modification combined intervention(PABM-intervention) on metabolic risk factors in overweight and obese elementary school children].

PubMed

Tak, Young-Ran; An, Ji-Yeon; Kim, Young-A; Woo, Hae-Young

2007-10-01

The purpose of this study was to identify the effects of a physical activity-behavior modification combined intervention(PABM-intervention) on metabolic risk factors in overweight and obese elementary school children. Thirty-two participants (BMI>or=85 percentile or relative obesity>or=10) were allocated to the PABM-intervention group and behavior modification only intervention group. The PABM-intervention was composed of exercise intervention consisting of 50 minutes of physical activity(Hip-hop dance & gym-based exercises) twice a week and the behavior modification intervention consisted of 50 minutes of instruction for modifying lifestyle habits(diet & exercise) once a week. Effectiveness of intervention was based on waist circumference, BP, HDL-cholesterol, TG, and fasting glucose before and after the intervention. The proportion of subjects with 1, 2, 3 or more metabolic risk factors were 28.1, 43.8, and 15.6%, respectively. After the 8-week intervention, waist circumference, systolic BP, diastolic BP, and HDL-cholesterol changed significantly(p<.01) in the PABM group. This provides evidence that a PABM-intervention is effective in changing metabolic risk factors such as waist circumference, systolic BP, diastolic BP, and HDL-cholesterol in overweight and obese elementary school children.

Surface Modification of Orthodontic Bracket Models via Ion Implantation: Effect on Coefficients of Friction

DTIC Science & Technology

1989-01-01

FEB 2 2 1990 Stephen Walter Andrews, D.M.D. The University of North Carolina at Chapel Hill Department of Orthodontics School of Dentistry 1989 Robert...PROJECT TASK WORK UNIT ELEMENT NO. NO. NO. ACCESSION NO. 11. TITLE (Include Security Classification) (UNCLASSIFIED) SURFACE MODIFICATION OF ORTHODONTIC ...Previous editions are obsolete. SECURITY CLASSIFICATION OF THIS PAGE AFIT/CI "OVERPRINT" SURFACE MODIFICATION OF ORTHODONTIC BRACKET MODELS VIA ION

Surface Modifications in Adhesion and Wetting

NASA Astrophysics Data System (ADS)

Longley, Jonathan

Advances in surface modification are changing the world. Changing surface properties of bulk materials with nanometer scale coatings enables inventions ranging from the familiar non-stick frying pan to advanced composite aircraft. Nanometer or monolayer coatings used to modify a surface affect the macro-scale properties of a system; for example, composite adhesive joints between the fuselage and internal frame of Boeing's 787 Dreamliner play a vital role in the structural stability of the aircraft. This dissertation focuses on a collection of surface modification techniques that are used in the areas of adhesion and wetting. Adhesive joints are rapidly replacing the familiar bolt and rivet assemblies used by the aerospace and automotive industries. This transition is fueled by the incorporation of composite materials into aircraft and high performance road vehicles. Adhesive joints have several advantages over the traditional rivet, including, significant weight reduction and efficient stress transfer between bonded materials. As fuel costs continue to rise, the weight reduction is accelerating this transition. Traditional surface pretreatments designed to improve the adhesion of polymeric materials to metallic surfaces are extremely toxic. Replacement adhesive technologies must be compatible with the environment without sacrificing adhesive performance. Silane-coupling agents have emerged as ideal surface modifications for improving composite joint strength. As these coatings are generally applied as very thin layers (<50 nm), it is challenging to characterize their material properties for correlation to adhesive performance. We circumvent this problem by estimating the elastic modulus of the silane-based coatings using the buckling instability formed between two materials of a large elastic mismatch. The elastic modulus is found to effectively predict the joint strength of an epoxy/aluminum joint that has been reinforced with silane coupling agents. This buckling

Assessment of Modifications for Improving Navigation at Hilo Harbor, Hawaii

DTIC Science & Technology

2016-06-01

ER D C/ CH L TR -1 6- 9 Coastal Inlets Research Program Assessment of Modifications for Improving Navigation at Hilo Harbor, Hawaii...at http://acwc.sdp.sirsi.net/client/default. Coastal Inlets Research Program ERDC/CHL TR-16-9 June 2016 Assessment of Modifications for Improving...validation with 2013–2014 field data ................................................. 86 4.5.3 Chile tsunami effect on Hilo Harbor

Efficient and accurate causal inference with hidden confounders from genome-transcriptome variation data

PubMed Central

2017-01-01

Mapping gene expression as a quantitative trait using whole genome-sequencing and transcriptome analysis allows to discover the functional consequences of genetic variation. We developed a novel method and ultra-fast software Findr for higly accurate causal inference between gene expression traits using cis-regulatory DNA variations as causal anchors, which improves current methods by taking into consideration hidden confounders and weak regulations. Findr outperformed existing methods on the DREAM5 Systems Genetics challenge and on the prediction of microRNA and transcription factor targets in human lymphoblastoid cells, while being nearly a million times faster. Findr is publicly available at https://github.com/lingfeiwang/findr. PMID:28821014

Surface modification of malachite with ethanediamine and its effect on sulfidization flotation

NASA Astrophysics Data System (ADS)

Feng, Qicheng; Zhao, Wenjuan; Wen, Shuming

2018-04-01

Ethanediamine was used to modify the mineral surface of malachite to improve its sulfidization and flotation behavior. The activation mechanism was investigated by adsorption experiments, X-ray photoelectron spectroscopy (XPS) analysis, and zeta potential measurements. Microflotation experiments showed that the flotation recovery of malachite was enhanced after the pretreatment of the mineral particles with ethanediamine prior to the addition of Na2S. Adsorption tests revealed that numerous sulfide ion species in the pulp solution were transferred onto the mineral surface through the formation of more copper sulfide species. This finding was confirmed by the results of the XPS measurements. Ethanediamine modification not only increased the contents of copper sulfide species on the malachite surface but also enhanced the reactivity of the sulfidization products. During sulfidization, Cu(II) species on the mineral surface were reduced into Cu(I) species, and the percentages of S22- and Sn2- relative to the total S increased after modification, resulting in increased surface hydrophobicity. The results of zeta potential measurements showed that the ethanediamine-modified mineral surface adsorbed with more sulfide ion species was advantageous to the attachment of xanthate species, thereby improving malachite floatability. The proposed ethanediamine modification followed by sulfidization xanthate flotation exhibits potential for industrial application.

Magnetic zenith effect in the ionospheric modification by an X-mode HF heater wave

NASA Astrophysics Data System (ADS)

Blagoveshchenskaya, N. F.; Borisova, T. D.; Haggstrom, I.; Rietveld, M. T.; Yeoman, T. K.

2013-12-01

We report experimental results aimed at an investigation of the magnetic zenith effect in the high latitude ionosphere F region from ionospheric modification by powerful HF heater wave with X-polarization. The ionospheric modification was produced by the HF heating facility at Tromsø (Norway) using the phased array with a narrow beam with of 6 degrees. Effective radiated power was varied between 450 and 1000 MW. The HF pump wave radiated in different directions relative to the magnetic field from 90 degrees (vertical) to 78 degrees (magnetic zenith) at frequencies near or above the ordinary-mode critical frequency. The response of the ionosphere plasma to the HF pump wave impact was checked by the UHF incoherent scatter radar located in the immediate vicinity of the HF heater. UHF radar was probing the plasma parameters, such as electron density and temperature (Ne and Te), HF-induced plasma and ion lines in the altitude range from 90 to 600 km. It was running in a scanning mode when UHF radar look angles were changed from 74 to 90 degrees by 1 or 2 degree step. It was clearly demonstrated that the strongest heater-induced effects took place in the magnetic field-aligned direction when HF pointing was also to the magnetic zenith. It was found that strong Ne enhancement of up to 80 % along magnetic field (artificial density ducts) were excited only under HF pumping towards magnetic zenith. The width of the artificial ducts comes to only 2 degrees. The Ne increases were accompanied by the Te enhancements of up to about 50 %. Less pronounced Te increases were also observed in the directions of 84 and 90 degrees. Strong Ne enhancements can be accompanied by excitation of strong HF-induced plasma and ion lines. Thus experimental results obtained points to the strong magnetic zenith effect due to self-focusing powerful HF radio wave with X-mode polarization.

On the Influence of Confounding Factors in Multisite Brain Morphometry Studies of Developmental Pathologies: Application to Autism Spectrum Disorder.

PubMed

Auzias, G; Takerkart, S; Deruelle, C

2016-05-01

Pooling data acquired on different MR scanners is a commonly used practice to increase the statistical power of studies based on MRI-derived measurements. Such studies are very appealing since they should make it possible to detect more subtle effects related to pathologies. However, the influence of confounds introduced by scanner-related variations remains unclear. When studying brain morphometry descriptors, it is crucial to investigate whether scanner-induced errors can exceed the effect of the disease itself. More specifically, in the context of developmental pathologies such as autism spectrum disorders (ASD), it is essential to evaluate the influence of the scanner on age-related effects. In this paper, we studied a dataset composed of 159 anatomical MR images pooled from three different scanners, including 75 ASD patients and 84 healthy controls. We quantitatively assessed the effects of the age, pathology, and scanner factors on cortical thickness measurements. Our results indicate that scan pooling from different sites would be less fruitful in some cortical regions than in others. Although the effect of age is consistent across scanners, the interaction between the age and scanner factors is important and significant in some specific cortical areas.

Histone modification: cause or cog?

PubMed

Henikoff, Steven; Shilatifard, Ali

2011-10-01

Histone modifications are key components of chromatin packaging but whether they constitute a 'code' has been contested. We believe that the central issue is causality: are histone modifications responsible for differences between chromatin states, or are differences in modifications mostly consequences of dynamic processes, such as transcription and nucleosome remodeling? We find that inferences of causality are often based on correlation and that patterns of some key histone modifications are more easily explained as consequences of nucleosome disruption in the presence of histone modifying enzymes. We suggest that the 35-year-old DNA accessibility paradigm provides a mechanistically sound basis for understanding the role of nucleosomes in gene regulation and epigenetic inheritance. Based on this view, histone modifications and variants contribute to diversification of a chromatin landscape shaped by dynamic processes that are driven primarily by transcription and nucleosome remodeling. Copyright © 2011 Elsevier Ltd. All rights reserved.

Characterization of organo-modified bentonite sorbents: The effect of modification conditions on adsorption performance

NASA Astrophysics Data System (ADS)

Parolo, María E.; Pettinari, Gisela R.; Musso, Telma B.; Sánchez-Izquierdo, María P.; Fernández, Laura G.

2014-11-01

The organic modification of a natural bentonite was evaluated using two methods: exchanging the interlayer cations by hexadecyltrimethylammonium (HDTMA) and grafting with vinyltrimethoxysilane (VTMS) and γ-methacryloyloxy propyl trimethoxysilane (TMSPMA) on montmorillonite surface. The physicochemical characterization of all materials was made by X-ray diffraction (XRD), IR spectroscopy, thermogravimetric analysis (TGA) and Brunauer-Emmett-Teller (BET) surface area techniques. HDTMA cations and organosilanes were intercalated into the interlayer space of montmorillonite, as deduced from the increase of the basal spacing. IR spectroscopy, TGA and BET area give evidence of successful organic modification. The studies show a decrease in the IR absorption band intensity at 3465 cm-1 with surfactant modification, and also a decrease of mass loss due to adsorbed water observed in two samples: the organoclay and functionalized bentonites, which are evidences of a lower interlayer hydrophilicity. The efficiency of aniline removal onto natural bentonite, organobentonite and functionalized bentonites from aqueous solutions was evaluated. Aniline sorption on natural bentonite was studied using batch experiments, XRD and IR spectroscopy. The hydrophobic surface of organobentonite and functionalized bentonites increased the retention capacity for nonionic organic substances such as aniline on bentonites. The sorption properties of modified bentonite, through different modification methods, enhanced the potential industrial applications of bentonites in water decontamination.

Do patient and practice characteristics confound age-group differences in preferences for general practice care? A quantitative study

PubMed Central

2013-01-01

Background Previous research showed inconsistent results regarding the relationship between the age of patients and preference statements regarding GP care. This study investigates whether elderly patients have different preference scores and ranking orders concerning 58 preference statements for GP care than younger patients. Moreover, this study examines whether patient characteristics and practice location may confound the relationship between age and the categorisation of a preference score as very important. Methods Data of the Consumer Quality Index GP Care were used, which were collected in 32 general practices in the Netherlands. The rank order and preference score were calculated for 58 preference statements for four age groups (0–30, 31–50, 51–74, 75 years and older). Using chi-square tests and logistic regression analyses, it was investigated whether a significant relationship between age and preference score was confounded by patient characteristics and practice location. Results Elderly patients did not have a significant different ranking order for the preference statements than the other three age groups (r = 0.0193; p = 0.41). However, in 53% of the statements significant differences were found in preference score between the four age groups. Elderly patients categorized significantly less preference statements as ‘very important’. In most cases, the significant relationships were not confounded by gender, education, perceived health, the number of GP contacts and location of the GP practice. Conclusion The preferences of elderly patients for GP care concern the same items as younger patients. However, their preferences are less strong, which cannot be ascribed to gender, education, perceived health, the number of GP contacts and practice location. PMID:23800156

Effect of lycopene and {beta}-carotene on peroxynitrite-mediated cellular modifications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muzandu, Kaampwe; Ishizuka, Mayumi; Sakamoto, Kentaro Q.

2006-09-15

Peroxynitrite formed by the reaction of superoxide and nitric oxide is a highly reactive species with a role in various pathological processes such as cancer, chronic inflammation, and cardiovascular and neurological diseases. In the present study, the effect of the carotenoids, lycopene and {beta}-carotene, on peroxynitrite-mediated modifications in plasmid DNA as well as cellular DNA and proteins were investigated. In pUC18 plasmid DNA, these carotenoids strongly inhibited DNA strand breaks caused by peroxynitrite generated from 3-morpholinosydnonimine (SIN-1). SIN-1 was also used to determine effects on DNA damage and protein tyrosine nitration in Chinese hamster lung fibroblasts. SIN-1 dose-dependently increased nitrationmore » of proteins in cells above basal levels as determined by Western blotting. This nitration was inhibited in the presence of the uric acid as well as lycopene. Physiological concentrations (0.31-10 {mu}M) of lycopene and {beta}-carotene also had protective effects on DNA damage, as measured by the comet assay. Lycopene significantly reduced DNA damage particularly, in the median range of concentrations (2.5 {mu}M). The protective effects of lycopene and {beta}-carotene could be due to their scavenging of reactive oxygen (ROS) and/or nitrogen species (RNS) as they reduce the amount of intracellular ROS/RNS produced following treatment with SIN-1 by as much as 47.5% and 42.4%, respectively. The results obtained in this study suggest that carotenoids may alleviate some of the deleterious effects of peroxynitrite and possibly other reactive nitrogen species as well in vivo.« less

Impact of acid and oxidative modifications, single or dual, of sorghum starch on biodegradable films.

PubMed

Biduski, Bárbara; Silva, Francine Tavares da; Silva, Wyller Max da; Halal, Shanise Lisie de Mello El; Pinto, Vania Zanella; Dias, Alvaro Renato Guerra; Zavareze, Elessandra da Rosa

2017-01-01

The objective of this study was to evaluate the effects of acid and oxidation modifications on sorghum starch, as well as the effect of dual modification of starch on the physical, morphological, mechanical, and barrier properties of biodegradable films. The acid modification was performed with 3% lactic acid and the oxidation was performed with 1.5% active chlorine. For dual modification, the acid modification was performed first, followed by oxidation under the same conditions as above. Both films of the oxidized starches, single and dual, had increased stiffness, providing a higher tensile strength and lower elongation when compared to films based on native and single acid modified starches. However, the dual modification increased the water vapor permeability of the films without changing their solubility. The increase in sorghum starch concentration in the filmogenic solution increased the thickness, water vapor permeability, and elongation of the films. Copyright © 2016. Published by Elsevier Ltd.

A review of the design and modification of lactoferricins and their derivatives.

PubMed

Hao, Ya; Yang, Na; Teng, Da; Wang, Xiumin; Mao, Ruoyu; Wang, Jianhua

2018-06-01

Lactoferricin (Lfcin), a multifunction short peptide with a length of 25 residues, is derived from the whey protein lactoferrin by acidic pepsin hydrolysis. It has potent nutritional enhancement, antimicrobial, anticancer, antiviral, antiparasitic, and anti-inflammatory activities. This review describes the research advantages of the above biological functions, with attention to the molecular design and modification of Lfcin. In this examination of design and modification studies, research on the identification of Lfcin active derivatives and crucial amino acid residues is also reviewed. Many strategies for Lfcin optimization have been studied in recent decades, but we mainly introduce chemical modification, cyclization, chimera and polymerization of this peptide. Modifications such as incorporation of D-amino acids, acetylation and/or amidation could effectively improve the activity and stability of these compounds. Due to their wide array of bio-functions and applications, Lfcins have great potential to be developed as biological agents with multiple functions involved with nutritional enhancement, as well as disease preventive and therapeutic effects.

Influence of Tooth Spacing Error on Gears With and Without Profile Modifications

NASA Technical Reports Server (NTRS)

Padmasolala, Giri; Lin, Hsiang H.; Oswald, Fred B.

2000-01-01

A computer simulation was conducted to investigate the effectiveness of profile modification for reducing dynamic loads in gears with different tooth spacing errors. The simulation examined varying amplitudes of spacing error and differences in the span of teeth over which the error occurs. The modification considered included both linear and parabolic tip relief. The analysis considered spacing error that varies around most of the gear circumference (similar to a typical sinusoidal error pattern) as well as a shorter span of spacing errors that occurs on only a few teeth. The dynamic analysis was performed using a revised version of a NASA gear dynamics code, modified to add tooth spacing errors to the analysis. Results obtained from the investigation show that linear tip relief is more effective in reducing dynamic loads on gears with small spacing errors but parabolic tip relief becomes more effective as the amplitude of spacing error increases. In addition, the parabolic modification is more effective for the more severe error case where the error is spread over a longer span of teeth. The findings of this study can be used to design robust tooth profile modification for improving dynamic performance of gear sets with different tooth spacing errors.

Biasogram: Visualization of Confounding Technical Bias in Gene Expression Data

PubMed Central

Krzystanek, Marcin; Szallasi, Zoltan; Eklund, Aron C.

2013-01-01

Gene expression profiles of clinical cohorts can be used to identify genes that are correlated with a clinical variable of interest such as patient outcome or response to a particular drug. However, expression measurements are susceptible to technical bias caused by variation in extraneous factors such as RNA quality and array hybridization conditions. If such technical bias is correlated with the clinical variable of interest, the likelihood of identifying false positive genes is increased. Here we describe a method to visualize an expression matrix as a projection of all genes onto a plane defined by a clinical variable and a technical nuisance variable. The resulting plot indicates the extent to which each gene is correlated with the clinical variable or the technical variable. We demonstrate this method by applying it to three clinical trial microarray data sets, one of which identified genes that may have been driven by a confounding technical variable. This approach can be used as a quality control step to identify data sets that are likely to yield false positive results. PMID:23613961

View of Soviet ionospheric modification research

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duncan, L.M.; Showen, R.L.

1990-10-01

We have reviewed and provided a technical assessment of Soviet research of the past five to ten years in ionospheric modification by high-power radio waves. This review includes a comprehensive survey of Soviet published literature, conference proceedings, and direct discussions with the involved Soviet researchers. The current state of the art for Soviet research in this field is evaluated, identifying areas of potential breakthrough discoveries, and discussing implications of this work for emerging technologies and future applications. This assessment is divided into the categories of basic research, advanced research, and applications. Basic research is further subdivided into studies of themore » modified natural geophysical environment, nonlinear plasma physics, and polar geophysical studies. Advanced research topics include the generation of artificial ionization mirrors and high-power oblique propagation effects. A separate comparative assessment of Soviet theoretical work also is included in this analysis. Our evaluation of practical and potential applications of this research discusses the utility of ionospheric modification in creating disturbed radio wave propagation environments, and its role in current and future remote-sensing and telecommunications systems. This technical assessment does not include consideration of ionospheric modification by means other than high-power radio waves. The Soviet effort in ionospheric modification sustains theoretical and experimental research at activity levels considerably greater than that found in comparable programs in the West. Notable strengths of the Soviet program are its breadth of coverage, large numbers of scientific participation, theoretical creativity and insight, and its powerful radio wave transmitting facilities.« less

Role of Oxidative Stress in Epigenetic Modification in Endometriosis.

PubMed

Ito, Fuminori; Yamada, Yuki; Shigemitsu, Aiko; Akinishi, Mika; Kaniwa, Hiroko; Miyake, Ryuta; Yamanaka, Shoichiro; Kobayashi, Hiroshi

2017-11-01

Aberrant DNA methylation and histone modification are associated with an increased risk of reproductive disorders such as endometriosis. However, a cause-effect relationship between epigenetic mechanisms and endometriosis development has not been fully determined. This review provides current information based on oxidative stress in epigenetic modification in endometriosis. This article reviews the English-language literature on epigenetics, DNA methylation, histone modification, and oxidative stress associated with endometriosis in an effort to identify epigenetic modification that causes a predisposition to endometriosis. Oxidative stress, secondary to the influx of hemoglobin, heme, and iron during retrograde menstruation, is involved in the expression of CpG demethylases, ten-eleven translocation, and jumonji (JMJ). Ten-eleven translocation and JMJ recognize a wide range of endogenous DNA methyltransferases (DNMTs). The increased expression levels of DNMTs may be involved in the subsequent downregulation of the decidualization-related genes. This review supports the hypothesis that there are at least 2 distinct phases of epigenetic modification in endometriosis: the initial wave of iron-induced oxidative stress would be followed by the second big wave of epigenetic modulation of endometriosis susceptibility genes. We summarize the recent advances in our understanding of the underlying epigenetic mechanisms focusing on oxidative stress in endometriosis.

Human Rights and Behavior Modification

ERIC Educational Resources Information Center

Roos, Philip

1974-01-01

Criticisms of behavior modification, which charge that it violates ethical and legal principles, are discussed and reasons are presented to explain behavior modification's susceptibility to attack. (GW)

Mini-Society vs. Token Economy: An Experimental Comparison of the Effects on Learning and Autonomy of Socially Emergent and Imposed Behavior Modification

ERIC Educational Resources Information Center

Kourilsky, Marilyn; Hirshleifer, Jack

1976-01-01

This study compares the effects of two teacher training programs designed to emphasize one of two forms of behavior modification in teaching economics to fourth-, fifth-, and sixth-grade pupils. (DMT)

Training teachers in generalized writing of behavior modification programs for multihandicapped deaf children.

PubMed

Hundert, J

1982-01-01

In contrast to previous studies where teachers were instructed how to implement behavior modification programs designed by an experimenter, teachers in the present experiment were taught how to write as well as implement behavior modification programs. The generalized effects of two training conditions on teacher and pupil behaviors were assessed by a multiple baseline design where, following baseline, two teachers of multi-handicapped deaf children were taught to set objectives and measure pupil performance (measurement training), Later, through a training manual, they learned a general problem-solving approach to writing behavior modification programs (programming training). After both training conditions, experimenter feedback was given for teachers' application of training to a target behavior for one pupil and generalization was measured across target behaviors for the same pupil and across pupils. It was found that measurement training had little general effect on either teacher behavior or pupil behavior. However, after programming training, teachers increased their program writing and correct use of behavior modification procedures and generalized this training across pupils and target behaviors. Along with these effects, there was improvement in pupil behaviors. Possible explanation for generalized effects of teacher training were considered.

Effect of surface modification and UVA photoactivation on antibacterial bioactivity of zinc oxide powder

NASA Astrophysics Data System (ADS)

Ann, Ling Chuo; Mahmud, Shahrom; Bakhori, Siti Khadijah Mohd; Sirelkhatim, Amna; Mohamad, Dasmawati; Hasan, Habsah; Seeni, Azman; Rahman, Rosliza Abdul

2014-02-01

The effects of surface modification of zinc oxide (ZnO) powder and UVA illumination on the powder towards Escherichia coli and Staphylococcus aureus were investigated. FESEM-EDS results showed that oxygen annealing increased the O:Zn ratio on the surface of ZnO-rod and ZnO-plate samples. Surface conductances of ZnO-rod and ZnO-plate pellets were reduced from 1.05 nS to 0.15 nS and 1.34 nS to 0.23 nS, respectively. Meanwhile, UVA illumination on the surface of the ZnO-rod and ZnO-plate samples was found to improve surface conductance to 7.08 nS and 6.51 nS, respectively, due to the release of charge carrier. Photoluminescence results revealed that oxygen annealing halved the UV emission intensity and green emission intensity, presumably caused by oxygen absorption in the ZnO lattice. The antibacterial results showed that oxygen-treated ZnO exhibited slightly higher growth inhibition on E. coli and S. aureus compared with unannealed ZnO. UVA illumination on ZnO causes the greatest inhibition toward E. coli and S. aureus. Under the UVA excitation, the inhibition of E. coli increased by 18% (ZnO-rod) and 13% (ZnO-plate) while the inhibition of S. aureus increased by 22% (ZnO-rod) and 21% (ZnO-plate). Release of reactive oxygen species were proposed in antibacterial mechanisms, which were aided by surface modification and UVA photoactivation. The reactive oxygen species disrupted the DNA and protein synthesis of the bacterial cell, causing bacteriostatic effects toward E. coli and S. aureus.

Asthma morbidity and ambient air pollution: effect modification by residential traffic-related air pollution.

PubMed

Delfino, Ralph J; Wu, Jun; Tjoa, Thomas; Gullesserian, Sevan K; Nickerson, Bruce; Gillen, Daniel L

2014-01-01

Ambient air pollution has been associated with asthma-related hospital admissions and emergency department visits (hospital encounters). We hypothesized that higher individual exposure to residential traffic-related air pollutants would enhance these associations. We studied 11,390 asthma-related hospital encounters among 7492 subjects 0-18 years of age living in Orange County, California. Ambient exposures were measured at regional air monitoring stations. Seasonal average traffic-related exposures (PM2.5, ultrafine particles, NOx, and CO) were estimated near subjects' geocoded residences for 6-month warm and cool seasonal periods, using dispersion models based on local traffic within 500 m radii. Associations were tested in case-crossover conditional logistic regression models adjusted for temperature and humidity. We assessed effect modification by seasonal residential traffic-related air pollution exposures above and below median dispersion-modeled exposures. Secondary analyses considered effect modification by traffic exposures within race/ethnicity and insurance group strata. Asthma morbidity was positively associated with daily ambient O3 and PM2.5 in warm seasons and with CO, NOx, and PM2.5 in cool seasons. Associations with CO, NOx, and PM2.5 were stronger among subjects living at residences with above-median traffic-related exposures, especially in cool seasons. Secondary analyses showed no consistent differences in association, and 95% confidence intervals were wide, indicating a lack of precision for estimating these highly stratified associations. Associations of asthma with ambient air pollution were enhanced among subjects living in homes with high traffic-related air pollution. This may be because of increased susceptibility (greater asthma severity) or increased vulnerability (meteorologic amplification of local vs. correlated ambient exposures).

Invited commentary: boundless science--putting natural direct and indirect effects in a clearer empirical context.

PubMed

Naimi, Ashley I

2015-07-15

Epidemiologists are increasingly using natural effects for applied mediation analyses, yet 1 key identifying assumption is unintuitive and subject to some controversy. In this issue of the Journal, Jiang and VanderWeele (Am J Epidemiol. 2015;182(2):105-108) formalize the conditions under which the difference method can be used to estimate natural indirect effects. In this commentary, I discuss implications of the controversial "cross-worlds" independence assumption needed to identify natural effects. I argue that with a binary mediator, a simple modification of the authors' approach will provide bounds for natural direct and indirect effect estimates that better reflect the capacity of the available data to support empirical statements on the presence of mediated effects. I discuss complications encountered when odds ratios are used to decompose effects, as well as the implications of incorrectly assuming the absence of exposure-induced mediator-outcome confounders. I note that the former problem can be entirely resolved using collapsible measures of effect, such as risk ratios. In the Appendix, I use previous derivations for natural direct effect bounds on the risk difference scale to provide bounds on the odds ratio scale that accommodate 1) uncertainty due to the cross-world independence assumption and 2) uncertainty due to the cross-world independence assumption and the presence of exposure-induced mediator-outcome confounders. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Genetic Control of the Secondary Modification of Deoxyribonucleic Acid in Escherichia coli1

PubMed Central

Mamelak, Linda; Boyer, Herbert W.

1970-01-01

The wild-type restriction and modification alleles of Escherichia coli K-12 and B were found to have no measurable effect on the patterns of methylated bases in the deoxyribonucleic acid (DNA) of these strains. The genetic region controlling the methylation of cytosine in E. coli K-12 was mapped close to his, and the presence or absence of this gene in E. coli B or E. coli K had no effect on the restriction and modification properties of these strains. Thus, only a few of the methylated bases in the DNA of these strains are involved in host modification, and the biological role of the remainder remains obscure. PMID:4919756

Synthetic Proteins and Peptides for the Direct Interrogation of α-Synuclein Posttranslational Modifications

PubMed Central

Pratt, Matthew R.; Abeywardana, Tharindumala; Marotta, Nicholas P.

2015-01-01

α-Synuclein is the aggregation-prone protein associated with Parkinson’s disease (PD) and related neurodegenerative diseases. Complicating both its biological functions and toxic aggregation are a variety of posttranslational modifications. These modifications have the potential to either positively or negatively affect α-synuclein aggregation, raising the possibility that the enzymes that add or remove these modifications could be therapeutic targets in PD. Synthetic protein chemistry is uniquely positioned to generate site-specifically and homogeneously modified proteins for biochemical study. Here, we review the application of synthetic peptides and proteins towards understanding the effects of α-synuclein posttranslational modifications. PMID:26120904

Effects of Harbor Modification on Crescent City, California's Tsunami Vulnerability

NASA Astrophysics Data System (ADS)

Dengler, Lori; Uslu, Burak

2011-06-01

More damaging tsunamis have impacted Crescent City, California in historic times than any other location on the West Coast of the USA. Crescent City's harbor has undergone significant modification since the early 20th century, including construction of several breakwaters, dredging, and a 200 × 300 m2 small boat basin. In 2006, a M w 8.3 earthquake in the Kuril Islands generated a moderate Pacific-wide tsunami. Crescent City recorded the highest amplitudes of any tide gauge in the Pacific and was the only location to experience structural damage. Strong currents damaged docks and boats within the small boat basin, causing more than US 20 million in damage and replacement costs. We examine how modifications to Crescent City's harbor may have affected its vulnerability to moderate tsunamis such as the 2006 event. A bathymetric grid of the basin was constructed based on US Army Corps of Engineers soundings in 1964 and 1965 before the construction of the small boat basin. The method of splitting tsunamis was used to estimate tsunami water heights and current velocities at several locations in the harbor using both the 1964-1965 grid and the 2006 bathymetric grid for the 2006 Kuril event and a similar-sized source along the Sanriku coast of Japan. Model velocity outputs are compared for the two different bathymetries at the tide gauge location and at six additional computational sites in the harbor. The largest difference between the two grids is at the small boat basin entrance, where the 2006 bathymetry produces currents over three times the strength of the currents produced by the 1965 bathymetry. Peak currents from a Sanriku event are comparable to those produced by the 2006 event, and within the boat basin may have been higher. The modifications of the harbor, and in particular the addition of the small boat basin, appear to have contributed to the high current velocities and resulting damage in 2006 and help to explain why the 1933 M w 8.4-8.7 Sanriku tsunami

Assessing the potential and side effects of ocean albedo modification in the Arctic

NASA Astrophysics Data System (ADS)

Mengis, N.; Oschlies, A.; Keller, D. P.; Martin, T.

2015-12-01

The ice albedo feedbacks in the Arctic are a key factor of the positive feedback mechanisms, which amplify climate change in the high northern latitudes. This study assesses the potential and side effects of an idealised Arctic ocean albedo modification (AOAM) experiment under varying emissions scenarios. A first finding is the fact that the decreasing trend in the Arctic summer sea ice extent could only be offset rather than reversed by the implementation of AOAM under increasing atmospheric CO2 emissions. What becomes evident in this study is that the Earth system regulates its internal heat budgets. Therefore a local cooling at the high northern latitudes causes compensatory heat fluxes in the atmosphere and the ocean. Meaning that firstly, the effectiveness of local scale climate intervention will, in the long term, be lowered by these compensatory fluxes and secondly that there are consequences, such as the subsurface warming signal found in this study, which are unexpected and unintended.

Quantification of the impact of a confounding variable on functional connectivity confirms anti-correlated networks in the resting-state.

PubMed

Carbonell, F; Bellec, P; Shmuel, A

2014-02-01

The effect of regressing out the global average signal (GAS) in resting state fMRI data has become a concern for interpreting functional connectivity analyses. It is not clear whether the reported anti-correlations between the Default Mode and the Dorsal Attention Networks are intrinsic to the brain, or are artificially created by regressing out the GAS. Here we introduce a concept, Impact of the Global Average on Functional Connectivity (IGAFC), for quantifying the sensitivity of seed-based correlation analyses to the regression of the GAS. This voxel-wise IGAFC index is defined as the product of two correlation coefficients: the correlation between the GAS and the fMRI time course of a voxel, times the correlation between the GAS and the seed time course. This definition enables the calculation of a threshold at which the impact of regressing-out the GAS would be large enough to introduce spurious negative correlations. It also yields a post-hoc impact correction procedure via thresholding, which eliminates spurious correlations introduced by regressing out the GAS. In addition, we introduce an Artificial Negative Correlation Index (ANCI), defined as the absolute difference between the IGAFC index and the impact threshold. The ANCI allows a graded confidence scale for ranking voxels according to their likelihood of showing artificial correlations. By applying this method, we observed regions in the Default Mode and Dorsal Attention Networks that were anti-correlated. These findings confirm that the previously reported negative correlations between the Dorsal Attention and Default Mode Networks are intrinsic to the brain and not the result of statistical manipulations. Our proposed quantification of the impact that a confound may have on functional connectivity can be generalized to global effect estimators other than the GAS. It can be readily applied to other confounds, such as systemic physiological or head movement interferences, in order to quantify their

Behavior Modification in the Classroom

ERIC Educational Resources Information Center

Whitman, Mryon; Whitman, Joan

1971-01-01

This article presents the theoretical rationale for behavior modification, principally through its comparison with traditional psychotherapies, and suggests some behavior modification techniques for the classroom management of maladaptive behavior. (Author)

Effect of surface topological structure and chemical modification of flame sprayed aluminum coatings on the colonization of Cylindrotheca closterium on their surfaces

NASA Astrophysics Data System (ADS)

Chen, Xiuyong; He, Xiaoyan; Suo, Xinkun; Huang, Jing; Gong, Yongfeng; Liu, Yi; Li, Hua

2016-12-01

Biofouling is one of the major problems for the coatings used for protecting marine infrastructures during their long-term services. Regulation in surface structure and local chemistry is usually the key for adjusting antifouling performances of the coatings. In this study, flame sprayed multi-layered aluminum coatings with micropatterned surfaces were constructed and the effects of their surface structure and chemistry on the settlement of typical marine diatoms were investigated. Micropatterned topographical morphology of the coatings was constructed by employing steel mesh as a shielding plate during the coating deposition. A silicone elastomer layer for sealing and interconnection was further brush-coated on the micropatterned coatings. Additional surface modification was made using zwitterionic molecules via DOPA linkage. The surface-modified coatings resist effectively colonization of Cylindrotheca closterium. This is explained by the quantitative examination of a simplified conditioning layer that deteriorated adsorption of bovine calf serum proteins on the zwitterionic molecule-treated samples is revealed. The colonization behaviors of the marine diatoms are markedly influenced by the micropatterned topographical morphology. Either the surface micropatterning or the surface modification by zwitterionic molecules enhances antimicrobial ability of the coatings. However, the combined micropatterned structure and zwitterionic modification do not show synergistic effect. The results give insight into anti-corrosion/fouling applications of the modified aluminum coatings in the marine environment.

Effect of Behavior Modification on Outcome in Early- to Moderate-Stage Chronic Kidney Disease: A Cluster-Randomized Trial.

PubMed

Yamagata, Kunihiro; Makino, Hirofumi; Iseki, Kunitoshi; Ito, Sadayoshi; Kimura, Kenjiro; Kusano, Eiji; Shibata, Takanori; Tomita, Kimio; Narita, Ichiei; Nishino, Tomoya; Fujigaki, Yoshihide; Mitarai, Tetsuya; Watanabe, Tsuyoshi; Wada, Takashi; Nakamura, Teiji; Matsuo, Seiichi

2016-01-01

Owing to recent changes in our understanding of the underlying cause of chronic kidney disease (CKD), the importance of lifestyle modification for preventing the progression of kidney dysfunction and complications has become obvious. In addition, effective cooperation between general physicians (GPs) and nephrologists is essential to ensure a better care system for CKD treatment. In this cluster-randomized study, we studied the effect of behavior modification on the outcome of early- to moderate-stage CKD. Stratified open cluster-randomized trial. A total of 489 GPs belonging to 49 local medical associations (clusters) in Japan. A total of 2,379 patients (1,195 in group A (standard intervention) and 1,184 in group B (advanced intervention)) aged between 40 and 74 years, who had CKD and were under consultation with GPs. All patients were managed in accordance with the current CKD guidelines. The group B clusters received three additional interventions: patients received both educational intervention for lifestyle modification and a CKD status letter, attempting to prevent their withdrawal from treatment, and the group B GPs received data sheets to facilitate reducing the gap between target and practice. The primary outcome measures were 1) the non-adherence rate of accepting continuous medical follow-up of the patients, 2) the collaboration rate between GPs and nephrologists, and 3) the progression of CKD. The rate of discontinuous clinical visits was significantly lower in group B (16.2% in group A vs. 11.5% in group B, p = 0.01). Significantly higher referral and co-treatment rates were observed in group B (p<0.01). The average eGFR deterioration rate tended to be lower in group B (group A: 2.6±5.8 ml/min/1.73 m2/year, group B: 2.4±5.1 ml/min/1.73 m2/year, p = 0.07). A significant difference in eGFR deterioration rate was observed in subjects with Stage 3 CKD (group A: 2.4±5.9 ml/min/1.73 m2/year, group B: 1.9±4.4 ml/min/1.73 m2/year, p = 0.03). Our care

Effect of Behavior Modification on Outcome in Early- to Moderate-Stage Chronic Kidney Disease: A Cluster-Randomized Trial

PubMed Central

Yamagata, Kunihiro; Makino, Hirofumi; Iseki, Kunitoshi; Ito, Sadayoshi; Kimura, Kenjiro; Kusano, Eiji; Shibata, Takanori; Tomita, Kimio; Narita, Ichiei; Nishino, Tomoya; Fujigaki, Yoshihide; Mitarai, Tetsuya; Watanabe, Tsuyoshi; Wada, Takashi; Nakamura, Teiji; Matsuo, Seiichi

2016-01-01

Objectives Owing to recent changes in our understanding of the underlying cause of chronic kidney disease (CKD), the importance of lifestyle modification for preventing the progression of kidney dysfunction and complications has become obvious. In addition, effective cooperation between general physicians (GPs) and nephrologists is essential to ensure a better care system for CKD treatment. In this cluster-randomized study, we studied the effect of behavior modification on the outcome of early- to moderate-stage CKD. Design Stratified open cluster-randomized trial. Setting A total of 489 GPs belonging to 49 local medical associations (clusters) in Japan. Participants A total of 2,379 patients (1,195 in group A (standard intervention) and 1,184 in group B (advanced intervention)) aged between 40 and 74 years, who had CKD and were under consultation with GPs. Intervention All patients were managed in accordance with the current CKD guidelines. The group B clusters received three additional interventions: patients received both educational intervention for lifestyle modification and a CKD status letter, attempting to prevent their withdrawal from treatment, and the group B GPs received data sheets to facilitate reducing the gap between target and practice. Main outcome measure The primary outcome measures were 1) the non-adherence rate of accepting continuous medical follow-up of the patients, 2) the collaboration rate between GPs and nephrologists, and 3) the progression of CKD. Results The rate of discontinuous clinical visits was significantly lower in group B (16.2% in group A vs. 11.5% in group B, p = 0.01). Significantly higher referral and co-treatment rates were observed in group B (p<0.01). The average eGFR deterioration rate tended to be lower in group B (group A: 2.6±5.8 ml/min/1.73 m2/year, group B: 2.4±5.1 ml/min/1.73 m2/year, p = 0.07). A significant difference in eGFR deterioration rate was observed in subjects with Stage 3 CKD (group A: 2.4±5.9 ml

Interpretational Confounding Is Due to Misspecification, Not to Type of Indicator: Comment on Howell, Breivik, and Wilcox (2007)

ERIC Educational Resources Information Center

Bollen, Kenneth A.

2007-01-01

R. D. Howell, E. Breivik, and J. B. Wilcox (2007) have argued that causal (formative) indicators are inherently subject to interpretational confounding. That is, they have argued that using causal (formative) indicators leads the empirical meaning of a latent variable to be other than that assigned to it by a researcher. Their critique of causal…

49 CFR 22.59 - Loan modifications.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Loan modifications. 22.59 Section 22.59 Transportation Office of the Secretary of Transportation SHORT-TERM LENDING PROGRAM (STLP) Loan Administration § 22.59 Loan modifications. Any modification to the terms of the DOT OSDBU guarantee agreement must...

Covalent modification of soy protein isolate by (-)-epigallocatechin-3-gallate: effects on structural and emulsifying properties.

PubMed

Tao, Fei; Jiang, He; Chen, Wenwei; Zhang, Yongyong; Pan, Jiarong; Jiang, Jiaxin; Jia, Zhenbao

2018-05-07

Soy protein isolate (SPI) has promising applications in various food products because of its excellent functional properties and nutritional quality. The structural and emulsifying properties of covalently modified SPI by (-)-epigallocatechin-3-gallate (EGCG) were investigated. SPI was covalently modified by EGCG under alkaline conditions. SDS-PAGE analysis revealed that EGCG modification caused cross-linking of SPI proteins. Circular dichroism spectra demonstrated that the secondary structure of SPI proteins was changed by EGCG modification. In addition, the modifications resulted in the perturbation of the tertiary structure of SPI as evidenced by intrinsic fluorescence spectra and surface hydrophobicity measurements. Oil-in-water emulsions of modified SPI had smaller droplet sizes and better creaming stability compared to those from unmodified SPI. The covalent modification by EGCG improved the emulsifying property of SPI. This study provided an innovative approach for improving the emulsifying properties of proteins. This article is protected by copyright. All rights reserved.

Epigenetic modifications by Trithorax group proteins during early embryogenesis: do members of Trx-G function as maternal effect genes?

PubMed

Andreu-Vieyra, Claudia; Matzuk, Martin M

2007-02-01

Maternal effect genes encode transcripts that are expressed during oogenesis. These gene products are stored in the oocyte and become functional during resumption of meiosis and zygote genome activation, and in embryonic stem cells. To date, a few maternal effect genes have been identified in mammals. Epigenetic modifications have been shown to be important during early embryonic development and involve DNA methylation and post-translational modification of core histones. During development, two families of proteins have been shown to be involved in epigenetic changes: Trithorax group (Trx-G) and Polycomb group (Pc-G) proteins. Trx-G proteins function as transcriptional activators and have been shown to accumulate in the oocyte. Deletion of Trx-G members using conventional knockout technology results in embryonic lethality in the majority of the cases analysed to date. Recent studies using conditional knockout mice have revealed that at least one family member is necessary for zygote genome activation. We propose that other Trx-G members may also regulate embryonic genome activation and that the use of oocyte-specific deletor mouse lines will help clarify their roles in this process.

Changes to histone modifications following prenatal alcohol exposure: An emerging picture.

PubMed

Chater-Diehl, Eric J; Laufer, Benjamin I; Singh, Shiva M

2017-05-01

Epigenetic mechanisms are important for facilitating gene-environment interactions in many disease etiologies, including Fetal Alcohol Spectrum Disorders (FASD). Extensive research into the role of DNA methylation and miRNAs in animal models has illuminated the complex role of these mechanisms in FASD. In contrast, histone modifications have not been as well researched, due in part to being less stable than DNA methylation and less well-characterized in disease. It is now apparent that even changes in transient marks can have profound effects if they alter developmental trajectories. In addition, many histone methylations are now known to be relatively stable and can propagate themselves. As technologies and knowledge have advanced, a small group has investigated the role of histone modifications in FASD. Here, we synthesize the data on the effects of prenatal alcohol exposure (PAE) on histone modifications. Several key points are evident. AS with most alcohol-induced outcomes, timing and dosage differences yield variable effects. Nevertheless, these studies consistently find enrichment of H3K9ac, H3K27me2,3, and H3K9me2, and increased expression of histone acetyltransferases and methyltransferases. The consistency of these alterations may implicate them as key mechanisms underlying FASD. Histone modification changes do not often correlate with gene expression changes, though some important examples exist. Encouragingly, attempts to reproduce specific histone modification changes are very often successful. We comment on possible directions for future studies, focusing on further exploration of current trends, expansion of time-point and dosage regimes, and evaluation of biomarker potential. Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical modification of chitosan for efficient gene therapy.

PubMed

Jiang, Hu-Lin; Cui, Peng-Fei; Xie, Rong-Lin; Cho, Chong-Su

2014-01-01

Gene therapy involves the introduction of foreign genetic material into cells in order to exert a therapeutic effect. Successful gene therapy relies on effective vector system. Viral vectors are highly efficient in transfecting cells, but the undesirable complications limit their therapeutic applications. As a natural biopolymer, chitosan has been considered to be a good gene carrier candidate due to its ideal character which combines biocompatibility, low toxicity with high cationic density together. However, the low cell specificity and low transfection efficiency of chitosan as a gene carrier need to be overcome before undertaking clinical trials. This chapter is principally on those endeavors such as chemical modifications using cell-specific ligands and stimuli-response groups as well as penetrating modifications that have been done to increase the performances of chitosan in gene therapy. © 2014 Elsevier Inc. All rights reserved.

Human germline genetic modification: scientific and bioethical perspectives.

PubMed

Smith, Kevin R; Chan, Sarah; Harris, John

2012-10-01

The latest mammalian genetic modification technology offers efficient and reliable targeting of genomic sequences, in the guise of designer genetic recombination tools. These and other improvements in genetic engineering technology suggest that human germline genetic modification (HGGM) will become a safe and effective prospect in the relatively near future. Several substantive ethical objections have been raised against HGGM including claims of unacceptably high levels of risk, damage to the status of future persons, and violations of justice and autonomy. This paper critically reviews the latest GM science and discusses the key ethical objections to HGGM. We conclude that major benefits are likely to accrue through the use of safe and effective HGGM and that it would thus be unethical to take a precautionary stance against HGGM. Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.

Antidepressant-Like Effects of Acupuncture-Insights From DNA Methylation and Histone Modifications of Brain-Derived Neurotrophic Factor.

PubMed

Jiang, Huili; Zhang, Xuhui; Lu, Jun; Meng, Hong; Sun, Yang; Yang, Xinjing; Zhao, Bingcong; Bao, Tuya

2018-01-01

Sensitive and stable biomarkers that facilitate depression detection and monitor the antidepressant efficiency are currently unavailable. Thus, the objective is to investigate the potential of DNA methylation and histone modifications of brain-derived neurotrophic factor (BDNF) in monitoring severity and antidepressive effects of acupuncture. The depression rat model was imitated by social isolation and chronic unpredicted mild stress (CUMS). The expression of serum BDNF was detected by enzyme-linked immunosorbent assay (ELISA), the hippocampal BDNF, acetylation levels in histone H3 lysine 9 (acH3K9), and HDAC2 by Western blot, the hippocampal mRNA of BDNF by RT-polymerase chain reaction (PCR). The DNA methylation patterns of the promoter I of BDNF was detected by MS-PCR. We investigated that the expression of BDNF in serum and hippocampus were significantly downregulated compared with controls. The same trend was found in mRNA of BDNF. Notably, acupuncture reversed the downregulation of BDNF in serum and hippocampus and mRNA of BDNF compared with model group. Acupuncture reversed the CUMS-induced downregulation of hippocampal acH3K9. On the contrary, the CUMS-induced upregulation of hippocampal HDAC2 in model group was significantly reversed by acupuncture. Collectively, the antidepressant effect of acupuncture might be mediated by regulating the DNA methylation and histone modifications of BDNF, which may represent novel biomaker for detection of depression and monitoring severity and antidepressive effects.

Alternative materials for subgrade modification

DOT National Transportation Integrated Search

2001-10-01

This study examines the laboratory and field performance of two alternative materials used for the modification of unstable (CBR<6) subgrade soils. Modification is temporarily enhancing subgrade : stability to improve the constructability of successi...

Effects of Ultrasonic Nanocrystal Surface Modification on the Residual Stress, Microstructure, and Corrosion Resistance of 304 Stainless Steel Welds

NASA Astrophysics Data System (ADS)

Ye, Chang; Telang, Abhishek; Gill, Amrinder; Wen, Xingshuo; Mannava, Seetha R.; Qian, Dong; Vasudevan, Vijay K.

2018-03-01

In this study, ultrasonic nanocrystal surface modification (UNSM) of 304 stainless steel welds was carried out. UNSM effectively eliminates the tensile stress generated during welding and imparts beneficial compressive residual stresses. In addition, UNSM can effectively refine the grains and increase hardness in the near-surface region. Corrosion tests in boiling MgCl2 solution demonstrate that UNSM can significantly improve the corrosion resistance due to the compressive residual stresses and changes in the near-surface microstructure.

Making the Mark: The Role of Adenosine Modifications in the Lifecycle of RNA Viruses

PubMed Central

Gonzales-van Horn, Sarah R.; Sarnow, Peter

2017-01-01

Summary Viral epitranscriptomics is a newly emerging field that has identified unique roles for RNA modifications in modulating lifecycles of RNA viruses. Despite the observation of a handful of modified viral RNAs five decades ago, very little was known about how these modifications regulate viral lifecycles, until recently. Here we review the pro- and anti-viral effects of methyl-6-adenosine in distinct viral life cycles, the role of 2′ O-methyl modifications in RNA stability and innate immune sensing, and functions of adenosine to inosine modifications in retroviral life cycles. With roles for over 100 modifications in RNA still unknown, this is a rapidly emerging field that is destined to suggest novel antiviral therapies. PMID:28618265

Proteomic Approaches to Quantify Cysteine Reversible Modifications in Aging and Neurodegenerative Diseases

PubMed Central

Gu, Liqing; Robinson, Renã A. S.

2016-01-01

Cysteine is a highly reactive amino acid and is subject to a variety of reversible post-translational modifications (PTMs), including nitrosylation, glutathionylation, palmitoylation, as well as formation of sulfenic acid and disulfides. These modifications are not only involved in normal biological activities, such as enzymatic catalysis, redox signaling and cellular homeostasis, but can also be the result of oxidative damage. Especially in aging and neurodegenerative diseases, oxidative stress leads to aberrant cysteine oxidations that affect protein structure and function leading to neurodegeneration as well as other detrimental effects. Methods that can identify cysteine modifications by type, including the site of modification, as well as the relative stoichiometry of the modification can be very helpful for understanding the role of the thiol proteome and redox homeostasis in the context of disease. Cysteine reversible modifications however, are challenging to investigate as they are low abundant, diverse, and labile especially under endogenous conditions. Thanks to the development of redox proteomic approaches, large-scale quantification of cysteine reversible modifications is possible. These approaches cover a range of strategies to enrich, identify, and quantify cysteine reversible modifications from biological samples. This review will focus on nongel-based redox proteomics workflows that give quantitative information about cysteine PTMs and highlight how these strategies have been useful for investigating the redox thiol proteome in aging and neurodegenerative diseases. PMID:27666938

Viral contacts confound studies of childhood leukemia and high-voltage transmission lines.

PubMed

Sahl, J D

1994-05-01

Studies of childhood leukemia have reported a link with residential proximity to electric utility facilities. This paper elaborates on the hypothesis that residential proximity to electric utility transmission-systems is a surrogate for viral contacts, a potential confounder in these studies. While the causal implications of increased viral contacts is not established, the assumption made here is that a significant component of childhood leukemia has an infectious etiology. Increased viral contacts can result from residential mobility, being first born, or use of community childcare facilities. Re-analysis of existing studies should look specifically for the interaction between childhood leukemia, markers for viral contacts (e.g., residential mobility, birth order, use of outside childcare facilities), and residential proximity to high-voltage transmission lines. New study designs should include parameters to test directly for a virus-related infectious model for childhood leukemia.

Different effects of bisphenol-A on memory behavior and synaptic modification in intact and estrogen-deprived female mice.

PubMed

Xu, Xiaohong; Gu, Ting; Shen, Qiaoqiao

2015-03-01

Bisphenol-A (BPA) has the capability of interfering with the effects of estrogens on modulating brain function. The purpose of this study was to investigate the effects of BPA on memory and synaptic modification in the hippocampus of female mice under different levels of cycling estrogen. BPA exposure (40, 400 μg/kg/day) for 8 weeks did not affect spatial memory and passive avoidance task of gonadally intact mice but improved ovariectomy (Ovx)-induced memory impairment, whereas co-exposure of BPA with estradiol benzoate (EB) diminished the rescue effect of EB on memory behavior of Ovx mice. The results of morphometric measurement showed that BPA positively modified the synaptic interface structure and increased the synaptic density of CA1 pyramidal cell in the hippocampus of Ovx females, but inhibited the enhancement of EB on synaptic modification and synaptogenesis of Ovx mice. Furthermore, BPA up-regulated synaptic proteins synapsin I and PSD-95 and NMDA receptor NR2B but inhibited EB-induced increase in PSD-95 and NR2B in the hippocampus of Ovx mice. These results suggest that BPA interfered with normal hormonal regulation in synaptic plasticity and memory of female mice as a potent estrogen mimetic and as a disruptor of estrogen under various concentrations of cycling estrogen. © 2014 International Society for Neurochemistry.

The histone modifications governing TFF1 transcription mediated by estrogen receptor.

PubMed

Li, Yanyan; Sun, Luyang; Zhang, Yu; Wang, Dandan; Wang, Feng; Liang, Jing; Gui, Bin; Shang, Yongfeng

2011-04-22

Transcription regulation by histone modifications is a major contributing factor to the structural and functional diversity in biology. These modifications are encrypted as histone codes or histone languages and function to establish and maintain heritable epigenetic codes that define the identity and the fate of the cell. Despite recent advances revealing numerous histone modifications associated with transcription regulation, how such modifications dictate the process of transcription is not fully understood. Here we describe spatial and temporal analyses of the histone modifications that are introduced during estrogen receptor α (ERα)-activated transcription. We demonstrated that aborting RNA polymerase II caused a disruption of the histone modifications that are associated with transcription elongation but had a minimal effect on modifications deposited during transcription initiation. We also found that the histone H3S10 phosphorylation mark is catalyzed by mitogen- and stress-activated protein kinase 1 (MSK1) and is recognized by a 14-3-3ζ/14-3-3ε heterodimer through its interaction with H3K4 trimethyltransferase SMYD3 and the p52 subunit of TFIIH. We showed that H3S10 phosphorylation is a prerequisite for H3K4 trimethylation. In addition, we demonstrated that SET8/PR-Set7/KMT5A is required for ERα-regulated transcription and its catalyzed H4K20 monomethylation is implicated in both transcription initiation and elongation. Our experiments provide a relatively comprehensive analysis of histone modifications associated with ERα-regulated transcription and define the biological meaning of several key components of the histone code that governs ERα-regulated transcription.

Ultrafast laser-induced modifications of energy bands of non-metal crystals

NASA Astrophysics Data System (ADS)

Gruzdev, Vitaly

2009-10-01

Ultrafast laser-induced variations of electron energy bands of transparent solids significantly influence ionization and conduction-band electron absorption driving the initial stage of laser-induced damage (LID). The mechanisms of the variations are attributed to changing electron functions from bonding to anti-bonding configuration via laser-induced ionization; laser-driven electron oscillations in quasi-momentum space; and direct distortion of the inter-atomic potential by electric field of laser radiation. The ionization results in the band-structure modification via accumulation of broken chemical bonds between atoms and provides significant contribution to the overall modification only when enough excited electrons are accumulated in the conduction band. The oscillations are associated with modification of electron energy by pondermotive potential of the oscillations. The direct action of radiation's electric field leads to specific high-frequency Franz-Keldysh effect (FKE) spreading the allowed electron states into the bands of forbidden energy. Those processes determine the effective band gap that is a laser-driven energy gap between the modified electron energy bands. Among those mechanisms, the latter two provide reversible band-structure modification that takes place from the beginning of the ionization and are, therefore, of special interest due to their strong influence on the initial stage of the ionization. The pondermotive potential results either in monotonous increase or oscillatory variations of the effective band gap that has been taken into account in some ionization models. The classical FKE provides decrease of the band gap. We analyzing the competition between those two opposite trends of the effective-band-gap variations and discuss applications of those effects for considerations of the laser-induced damage and its threshold in transparent solids.

The effect of habitat modification on plant-pollinator network

NASA Astrophysics Data System (ADS)

Aminatun, Tien; Putra, Nugroho Susetya

2017-08-01

The research aimed to determine; (1) the mutualism interaction pattern of plant-pollinator on several habitat modifications; and (2) the habitat modification which showed the most stable pattern of interaction. The study was conducted in one planting season with 20 plots which each plot had 2x2 m2 width and 2 m spacing among plots, and each plot was planted with the same variety of tomato plants, i.e. "intan". Nitrogen manipulation treatment was conducted with four kinds of fertilizers, i.e. NPK (code PU), compost (code PKM), vermicompost (code PC), and manure (code PK). Each treatment had 5 plot replications. We observed the growth of tomato plants, weed and arthropod populationstwo weekly while pollinator visitation twice a week during tomato plant flowering with counting population and visitation frequence of each pollinator on each sample of tomato plants. The nectar of tomato plant flower of each treatment was tested in laboratory to see its reducing sugar and sucrose. Oganic matter and nitrogen of the soil samples of each treatment were tested in laboratory in the beginning and the end of this research. We analized the plant-pollinator network with bipartite program in R-statistics, and the abiotic and other biotic factors with descriptive analysis. The results of the research were; (1) the mutualism interaction pattern of plant-pollinator network of four treatments were varied, and (2) The pattern of plant-pollinator network of NPK fertilizer treatment showed the more stable interaction based on analysis of interaction evenness, Shannon diversity, frequency and longevity of pollinator visitation.

Effects of initial saturation on properties modification and displacement of tetrachloroethene with aqueous isobutanol.